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Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain
(Correspondence should be addressed to M Ferrer; Email: mercedes.ferrer{at}uam.es)
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Abstract |
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Introduction |
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Vascular tone is regulated by several mechanisms in which, depending on the type of the vessel, innervation plays a more or less important role. This regulation involves the adrenergic, cholinergic, nitrergic, peptidergic, and/or sensory innervations (Vanhoutte et al. 1981, Marco et al. 1985, Kawasaki et al. 1988) that are specific to the vascular bed under consideration. Nitric oxide (NO) is an important neurotransmitter in both the central (Bredt et al. 1992) and peripheral (Marín & Balfagón 1998) nervous systems. Electrical field stimulation (EFS) has been shown to induce NO release from nitrergic nerves in rat mesenteric arteries (Marín & Balfagón 1998, Ferrer et al. 2000, Ferrer & Balfagón 2001, del Carmen Martín et al. 2005), thus producing relaxation by stimulating soluble guanylate cyclase and increasing the intracellular levels of cGMP in the smooth muscle cells of the arterial wall (Holzmann 1982, Ignarro & Kadowitz 1985). Sex hormones have been described to modulate the release and/or function of the neuronal NO in male (del Carmen Martín et al. 2005) and female (Minoves et al. 2002) rat mesenteric arteries.
Vascular tone is also regulated by prostanoids originated by arachidonic acid metabolism through the cyclooxygenase pathway (Henrion et al. 1997, Blanco-Rivero et al. 2005, Félétou & Vanhoutte 2006). One of the most studied prostanoids is thromboxane A2 (TXA2) that has been implicated as a mediator in diseases such as myocardial infarction, hypertension and stroke (FitzGerald et al. 1987, Narumiya et al. 1999). We previously reported that, in mesenteric artery from comparable rats, endogenous male sex hormones modulate endothelial TXA2 production, whether in basal conditions or after stimulation with either clonidine (Blanco-Rivero et al. 2006a) or acetylcholine (Blanco-Rivero et al. 2007), without modifying the TXA2 vasoconstrictor effect. Additionally, we have also shown that endogenous male sex hormones regulate the functional involvement of endogenous TXA2 in vascular responses of aorta (Martorell et al. 2008) and mesenteric artery (Blanco-Rivero et al. 2006a, 2007).
On the other hand, while NO has been reported to modulate the prostanoid system (Salvemini et al. 1996, Laemmel et al. 2003), there have been few reports on the action of prostanoids on the NO system (Ferrer et al. 2004, Mollace et al. 2005). Moreover, regarding the specific action of TXA2 on the NO system, a decrease in inducible (Yamada et al. 2003) as well as endothelial (Miyamoto et al. 2007) NO release has been reported. However, details about the action of TXA2 on neuronal NO release in vascular tissue remain unknown.
In the light of these considerations, the present study was designed to investigate whether endogenous male sex hormones influence the release of TXA2 and the role of the latter in the EFS-induced response, as well as the mechanism involved in this response.
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Materials and Methods |
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Male Sprague–Dawley rats (6 months old) were used. Animals were housed in the Animal Facility of the Universidad Autónoma de Madrid (registration number EX-021U) in accordance with directives 609/86 CEE and RD 233/88 of the Ministerio de Agricultura, Pesca y Alimentación of Spain. Deprivation of male sex hormones was induced by gonadectomy at 7 weeks of age, and 4 months later the animals were killed. The observation of seminal vesicles atrophy confirmed successful surgery. The rats were weighed and killed by CO2 inhalation; the first branch of the mesenteric artery was carefully dissected out, cleaned of connective tissue, and placed in Krebs–Henseleit solution (KHS; in mM: NaCl, 115; CaCl2, 2.5; KCl, 4.6; KH2PO4, 1.2; MgSO4.7H2O, 1.2; NaHCO3, 25; glucose, 11.1; Na2 EDTA, 0.03) at 4 °C. The endothelium was removed to eliminate the main source of vasoactive substances, including NO. This avoided possible actions on endothelial cells by different drugs that could lead to misinterpretation of results. The endothelium was removed by gently rubbing the luminal surface of the segments with a thin wooden stick. The investigation conforms with the Guide for the Care and Use of Laboratory Animals published by the USA National Institutes of Health (publication no. 85.23 revised 1985).
TXA2, norepinephrine (NA), and prostaglandin I2 (PGI2) release
The production of TXA2 and PGI2 in vivo was typically monitored by measuring their stable metabolites TXB2 and 6-keto-PGF1
respectively, using a TXB2 or a 6-keto-PGF1 EIA kit (Cayman Chemical, Annator, MI, USA). NA was measured using Noradrenaline Research EIA (Labor Diagnostika Nord, Nordhom, Germany).
The endothelium-denuded rat mesenteric segments were preincubated for 30 min in 5 ml KHS at 37 °C, continuously gassed with a 95% O2–5% CO2 mixture (stabilization period). After several 10-min washout periods in a bath containing 400 µl KHS, the medium was collected to measure basal release. Once the chamber was refilled, cumulative EFS periods of 30 s at 1, 2, 4, 8, and 16 Hz at 1-min intervals were applied, and the medium was collected to measure the EFS-induced release. Each assay was performed following the manufacturer's instructions. Results were expressed as pg/ml x mg tissue for TXA2 and PGI2 release and as ng/ml x mg tissue for NA release.
Vascular reactivity
The method used for isometric tension recording has been described in full elsewhere (Nielsen & Owman 1971). Briefly, two parallel stainless steel pins were introduced through the lumen of the vascular segment: one was fixed to the bath wall and the other connected to a force transducer (Grass FTO3C; Quincy, MA, USA); this was connected in turn to a model 7D Grass polygraph. For the EFS experiments, the segments were mounted between two platinum electrodes 0.5 cm apart and connected to a stimulator (Grass, model S44) modified to supply appropriate current strength. The segments were suspended in an organ bath containing 5 ml KHS at 37 °C continuously bubbled with a 95% O2–5% CO2 mixture (pH 7.4). The segments were subjected to a tension of 0.5 g, which was readjusted every 15 min during a 90-min equilibration period before drug administration. After this, the vessels were exposed to 75 mM KCl to check their functional integrity. The endothelium removal did not alter the contractions elicited by 75 mM KCl. After a washout period, the absence of vascular endothelium was tested by the inability of 10 µM acetylcholine (ACh) to relax segments precontracted with 1 µM NA.
Frequency–response curves for EFS (1, 2, 4, 8, and 16 Hz) and concentration–response curves for NA (10 nM–10 µM) were obtained. The parameters used for EFS were 200 mA, 0.3 ms, and 1–16 Hz, for 30 s with an interval of 1 min between each stimulus, the time required to recover basal tone. A washout period of at least 1 h was necessary to avoid desensitization between consecutive curves. Three successive frequency–response curves separated by 1-h intervals produced similar contractile responses.
To determine the effect of endogenous TXA2 on the response induced by EFS, the TXA2 synthase inhibitor, furegrelate (1 µM), was added to the bath 30 min before the second frequency–response curve.
To determine the possible effect of endogenous TXA2 on the NA-induced vasoconstrictor response, furegrelate was added to the bath 30 min before performing the NA concentration–response curve. The possible effect of furegrelate on the vasodilator effect of NO was also analyzed by obtaining concentration–response curves for the NO donor sodium nitroprusside (SNP) in 30-min furegrelate preincubated arteries.
NO release
Endothelium-denuded mesenteric arteries from control and orchidectomized rats were subjected to a resting tension of 0.5 g as indicated for the reactivity experiments. After an equilibration period of 60 min, arteries were incubated with the fluorescent probe 4,5-diaminofluorescein (DAF-2, 0.5 µM) for 45 min. Then the medium was collected to measure basal NO release. Once the organ bath was refilled, cumulative EFS periods of 30 s at 1, 2, 4, 8, and 16 Hz at 1-min intervals were applied. The fluorescence of the medium was measured at room temperature using a spectrofluorimeter (LS50 Perkin–Elmer instruments; FL WinLab Software) with excitation wavelength set at 495 nm and emission wavelength at 515 nm. This method has been validated by comparing the results obtained with DAF and with those obtained by nitrites measurement (del Carmen Martín et al. 2005).
The interference of endogenous TXA2 on NO release was studied by incubating the arteries with the TXA2 synthase inhibitor furegrelate (1 µM) 30 min before collecting medium.
Each data was calculated by subtracting the blank measures from the corresponding NO release obtained. Blank measures were collected in the same way from segment-free medium in order to subtract background emission. The specificity of the method has already been demonstrated (del Carmen Martín et al. 2005, Blanco-Rivero et al. 2006c). The amount of NO released was expressed as arbitrary units/mg tissue.
Drugs
L-NA hydrochloride, ACh chloride, L-NAME hydrochloride, SNP and DAF-2 were obtained from Sigma–Aldrich and furegrelate from Cayman chemical (Europe). Stock solutions (10 mM) of drugs were made in distilled water, except for NA, which was dissolved in an NaCl (0.9%)–ascorbic acid (0.01% w/v) solution. These solutions were kept at –20 °C and appropriate dilutions were made in KHS on the day of the experiment.
Data analysis
The responses elicited by EFS or NA were expressed as a percentage of the contraction induced by 75 mM KCl. The relaxation induced by SNP was expressed as a percentage of the initial contraction elicited by 1 µM NA. Results are given as mean±S.E.M. Statistical analysis was done by comparing the curve obtained in the presence of the different substances with the previous or control curve by means of repeated-measures ANOVA. For the experiments on TXA2, NO, NA, and PGI2 release, the statistical analysis was done using Student's t-test for unpaired experiments. P<0.05 was considered significant.
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Results |
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Orchidectomy slightly decreased rat body weight (control, 469.7±8.4 g; orchidectomized, 428±5.4 g; n=10; P<0.05), but this did not affect the size of mesenteric artery.
TXA2 release
Orchidectomy increased basal TXA2 release. The EFS-induced TXA2 release was greater in arteries from orchidectomized than control male rats (Fig. 1).
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Preincubation with the TXA2 synthase inhibitor furegrelate (1 µM) did not modify basal tone in arteries from either rat group; furegrelate decreased the EFS-induced contraction in arteries from control male rats (Fig. 2a), but did not modify it in arteries from orchidectomized rats (Fig. 2b).
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Basal and EFS-induced NO release was similar in mesenteric arteries from both control and orchidectomized male rats (ANOVA, P>0.05). In segments from control male rats, preincubation with the TXA2 synthase inhibitor, furegrelate, did not modify the basal NO release, but did increase the EFS-induced NO release (Fig. 5a). By contrast, in segments from orchidectomized rats, preincubation with furegrelate did not affect the basal or EFS-induced NO release (Fig. 5b); similar results were obtained when the furegrelate concentration was increased to 10 µM (Fig. 5b).
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Basal and EFS-induced NA release was similar in mesenteric arteries from both control and orchidectomized male rats (ANOVA, P>0.05), as already reported using the tritium release method for measuring NA release (Blanco-Rivero et al. 2006c). The presence of furegrelate did not modify either the basal or the EFS-induced NA release in arteries from control (Fig. 6a) or orchidectomized (Fig. 6b) rats.
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Basal and EFS-induced PGI2 release was similar in mesenteric arteries from both control and orchidectomized male rats (ANOVA, P>0.05). Furegrelate did not modify this release in arteries from control rats (Fig. 7a), but increased it in arteries from orchidectomized rats (Fig. 7b).
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Discussion |
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The role of NO and prostanoids in regulating vascular tone is well established (Henrion et al. 1997, Ferrer & Osol 1998, Busse & Fleming 2003), and interaction between these two systems has been described, particularly that of NO acting on prostanoids release (Laemmel et al. 2003, Mollace et al. 2005); however, reports describing the action of prostanoids on the NO system are scarce (Ferrer et al. 2004). TXA2 is one of the most important vasoconstrictor prostanoids with stimulatory action on proliferation or hypertrophy of vascular smooth muscle cells (Hanasaki et al. 1990), and is implicated as a mediator in diseases such as myocardial infarction, hypertension, and stroke (FitzGerald et al. 1987, Narumiya et al. 1999). We previously reported that endothelial TXA2 release in mesenteric artery (Blanco-Rivero et al. 2006a, 2007) and aorta (Martorell et al. 2008) was increased in arteries from orchidectomized rats. The fact that the levels of testosterone dramatically decreased in orchidectomized rats (Martorell et al. 2008) seems to indicate that the vascular effects observed are testosterone dependent. However, the involvement of hormones and/or gonadal factors other than testosterone cannot be ruled out. Thus, vascular endothelial growth factor, basic fibroblast growth factor, transforming growth factor-β, or hyalurodinase with gonadal origin (Lissbrant et al. 2003) could all play an important role in vascular function (Rahmanian & Heldin 2002).
Therefore, we studied the possible modification of EFS-induced TXA2 release by endogenous male sex hormones. We found that orchidectomy increased the basal TXA2 release, as previously reported in endothelium intact mesenteric arteries from comparable animals (Blanco-Rivero et al. 2006a, 2007); it is important to mention that basal release in arteries without endothelium was lower than that in arteries with intact endothelium, confirming endothelial and smooth muscle cells as sources of TXA2 production.
We have previously demonstrated that EFS induced similar contractile responses in mesenteric arteries from control and orchidectomized rats, responses that appear to be mediated by NA release from adrenergic nerve terminals and the subsequent activation of -adrenoceptors (del Carmen Martín et al. 2005); in addition, we found that the contractile response to exogenous NA was decreased by orchidectomy (del Carmen Martín et al. 2005), suggesting that EFS could increase NA release in arteries from orchidectomized rats; however, we later demonstrated that the EFS-induced NA release was not modified by orchidectomy (Blanco-Rivero et al. 2006c), which indicates that other vasoconstrictor factors could be released when the artery was electrically stimulated. Since the EFS-induced release of TXA2 has been demonstrated in hypertensive rats (Aras-López et al. 2007), we analyzed the EFS-induced TXA2 release in normotensive rats, as well as the possible role of endogenous male sex hormones in that release. We observed that EFS induced a greater TXA2 formation in arteries from orchidectomized than control rats, which is in line with reports showing increased TXA2 release after activation of different receptors (Blanco-Rivero et al. 2006a, 2007). This result also indicates that TXA2 could be the contractile factor that is released when the artery is electrically stimulated, as suggested previously (Blanco-Rivero et al. 2006c). Increased TXA2 release would explain the non-modification of the EFS-induced response in arteries from control and orchidectomized rats, in spite of the fact that the NA response was diminished in arteries from the latter animals.
The next step was to analyze the function of endogenous TXA2 in the EFS-induced response, as well as the dependence on male sex hormones. Preincubation with furegrelate did not modify the basal tone in arteries from control or orchidectomized rats, indicating that endogenous TXA2 does not have a direct effect on vascular tone regulation in basal conditions. We showed that furegrelate decreased the EFS-induced response in arteries from control rats, but did not modify it in arteries from orchidectomized rats, indicating that the effect of endogenous TXA2 on the EFS response is under male sex hormone regulation.
It is widely reported that mesenteric arteries possess nitrergic (Marín & Balfagón 1998, del Carmen Martín et al. 2005), sympathetic (Li & Duckles 1992), and sensory (Kawasaki et al. 1988) innervations that modulate vasomotor tone; therefore, the EFS-induced contraction is the result of a balance between opposing vasoconstrictor and vasodilator factors (Vanhoutte 1996, Ferrer & Balfagón 2001). Since, in our experimental conditions, we have demonstrated that sensory innervation did not modulate the vasomotor response to EFS (del Carmen Martín et al. 2005); we studied whether the differences in the EFS-induced contractions observed in the presence of furegrelate were due to alterations in nitrergic and adrenergic innervations.
Since there is a lack of studies analyzing the effect of TXA2 on neuronal NO release, and since we previously reported that endogenous prostanoids different from TXA2, i.e. PGI2 increased neuronal NO release (Ferrer et al. 2004), it is possible to speculate that endogenous TXA2 could regulate neuronal NO and vasomotor function. Therefore, we studied the effect of the TXA2 synthesis inhibitor furegrelate, on the release and function of neuronal NO, as well as the dependence on endogenous male sex hormones. We found that in arteries from control rats, furegrelate increased the neuronal NO release, which is in line with reports describing an inhibitory effect of TXA2 on inducible (Yamada et al. 2003) and endothelial (Miyamoto et al. 2007) NO release. The vasodilator response induced by the NO donor, SNP, was also increased by furegrelate, showing that endogenous TXA2 negatively modulates both the release and the vasodilator effect of neuronal NO. These results could also explain the decreased the EFS-induced contraction in the presence of furegrelate, but alterations in the release and function of neurotransmitters other than NO cannot be ruled out.
Different modulating effects of TXA2 on NA release have been reported, including inhibition (Nishihara et al. 2000) and non-modification (Rump & Schollmeyer 1989). The fact that furegrelate did not modify either NA release or its vasomotor response, as reported previously (Molderings et al. 1998, Hoang et al. 2003), indicates that endogenous TXA2 does not alter the function of sympathetic innervation in arteries from control rats.
By contrast, in arteries from orchidectomized rats, furegrelate did not modify the basal and EFS-induced NO release; since TXA2 formation was greater in arteries from orchidectomized than control rats, we used a higher concentration of furegrelate, and still obtained similar results. In addition, the vasodilator response induced by SNP was not modified by furegrelate. These results show that endogenous TXA2 does not regulate the release or function of neuronal NO in arteries from orchidectomized rats, in contrast to what occurs in arteries from control rats.
Regarding noradrenergic neurotransmission, we found that furegrelate modified neither the NA release nor the vasoconstrictor response induced by exogenous NA, indicating that the function of the sympathetic innervation is not regulated by endogenous TXA2 in arteries from orchidectomized rats, as was also observed in arteries from control rats.
Since TXA2 was higher in arteries from orchidectomized rats, and since endogenous TXA2 did not modify either the release or function of NO or NA, the unaltered EFS-induced response observed in the presence of furegrelate could be explained through the release of vasodilator factors that would counterbalance the vasoconstrictor effect of TXA2.
One of the more plausible candidates would be PGI2, since crosstalk between TXA2 and PGI2 systems has been reported (Cheng et al. 2002, Martorell et al. 2008) and joint increases in PGI2 and TXA2 synthesis have been shown in pathological conditions (FitzGerald 1991, Caughey et al. 2001). Therefore, we measured the production of PGI2 in the presence of furegrelate in mesenteric arteries from both control and orchidectomized rats. First, we found that orchidectomy did not modify either the basal or EFS-induced PGI2 release, in contrast to the increased PGI2 formation observed in aorta from comparable animals (Martorell et al. 2008); these results are in line with reports showing smooth muscle (Wang et al. 1993, Ferrer et al. 2004) and/or neuronal (Snitsarev et al. 2005) cells as cellular sources of PGI2. Concerning the effect of endogenous TXA2 on PGI2 production, we observed that the inhibition of the endogenous TXA2 synthesis did not modify the release of PGI2 in arteries from control rats, although it did increase PGI2 release in arteries from orchidectomized rats. This result reinforced the suggestion that the possible increase in the release of vasodilator substances that counterbalance the vasoconstrictor effect of TXA2, although the involvement of substances other than PGI2 cannot be ruled out.
In summary, this study demonstrates that non-endothelial TXA2 release is increased in mesenteric arteries from orchidectomized rats. The effect of endogenous TXA2 on the EFS-induced response is also regulated in a gonad-dependent way, suggesting that male sex hormones modulate different simultaneous cell signaling pathways. In arteries from control rats, inhibition of TXA2 formation decreases the EFS-induced response by increasing neuronal NO release, but in arteries from orchidectomized rats, the EFS-induced response is unaltered after the inhibition of TXA2 formation, by increasing PGI2 release.
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Acknowledgements |
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References |
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Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H & Christiansen C 1999 Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. Circulation Research 84 813–819.
Aras-Lopéz R, Blanco-Rivero J, Xavier FE, Salaices M, Ferrer M & Balfagón G 2007 Dexamethasone decreases contraction to electrical field stimulation in mesenteric arteries from spontaneously hypertensive rats through decreases in thromboxane A2 release. Journal of Pharmacological and Experimental Therapeutics 322 1129–1136.
Blanco-Rivero J, Cachofeiro V, Lahera V, Aras-Lopez R, Márquez-Rodas I, Salaices M, Xavier FE, Ferrer M & Balfagón G 2005 Participation of prostacyclin in endothelial dysfunction induced by aldosterone in normotensive and hypertensive rats. Hypertension 46 107–112.
Blanco-Rivero J, Balfagón G & Ferrer M 2006a Orchidectomy modulates 2-adrenoceptor reactivity in rat mesenteric artery through increased Tromboxane A2 formation. Journal of Vascular Research 43 101–108.[CrossRef][Web of Science][Medline]
Blanco-Rivero J, Sagredo A, Balfagón G & Ferrer M 2006b Orchidectomy increases expression and activity of Cu/Zn-superoxide dismutase, while decreasing endothelial nitric oxide bioavailability. Journal of Endocrinology 190 771–778.
Blanco-Rivero J, Aras-López R, Del Campo L, Sagredo A, Balfagón G & Ferrer M 2006c Orchidectomy increases beta-adrenoceptor activation-mediated neuronal nitric oxide and noradrenaline release in rat mesenteric artery. Neuroendocrinology 84 378–385.[CrossRef][Web of Science][Medline]
Blanco-Rivero J, Sagredo A, Balfagón G & Ferrer M 2007 Protein kinase C activation increases endothelial nitric oxide release in mesenteric arteries from orchidectomized rats. Journal of Endocrinology 192 189–197.
Bredt DS, Ferris CD & Snyder SH 1992 Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites. Journal of Biological Chemistry 267 10976–10981.
Busse R & Fleming I 2003 Regulation of endothelium-derived vasoactive autacoid production by hemodynamic forces. Trends in Pharmacological Sciences 24 24–29.[CrossRef][Medline]
del Carmen Martín M, Balfagón G, Minoves N, Blanco-Rivero J & Ferrer M 2005 Androgens deprivation increases neuronal nitric oxide metabolism and its asodilatador efect in rat mesenteric arteries. Nitric Oxide 12 163–176.[CrossRef][Web of Science][Medline]
Caughey GE, Cleland LG, Gamble JR & James MJ 2001 Up-regulation of endothelial cyclooxygenase-2 and prostanoid synthesis by platelets. Role of thromboxane A2. Journal of Biological Chemistry 276 37839–37845.
Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T, Lawson JA & FitzGerald GA 2002 Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 296 539–541.
Félétou M & Vanhoutte PM 2006 Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). American Journal of Physiology. Heart and Circulatory Physiology 291 985–1002.[CrossRef]
Ferrer M & Balfagón G 2001 Aging alters neuronal nitric oxide release from eat mesenteric arteries: role of presinaptic β-adrenoreceptors. Clinical Science 101 321–328.[CrossRef][Web of Science][Medline]
Ferrer M & Osol G 1998 Estrogen replacement modulates resistance artery smooth muscle and endothelial alpha2-adrenoceptor reactivity. Endothelium 6 133–141.[Web of Science][Medline]
Ferrer M, Marín J & Balfagón G 2000 Diabetes alters neuronal nitric oxide release from rat mesenteric arteries: role of protein kinase C. Life Sciences 66 337–345.[Web of Science][Medline]
Ferrer M, Salaices M & Balfagón G 2004 Endogenous prostacyclin increases neuronal nitric oxide release in mesenteric artery from spontaneously hypertensive rats. European Journal of Pharmacology 506 151–156.[CrossRef][Web of Science][Medline]
FitzGerald GA 1991 Mechanisms of platelet activation: thromboxane A2 as an amplifying signal for other agonists. American Journal of Cardiology 68 11–15.[CrossRef]
FitzGerald GA, Healy C & Daugherty J 1987 Thromboxane A2 biosynthesis in human disease. Federation Proceedings 46 154–158.[Web of Science][Medline]
Hanasaki K, Nakano T & Arita H 1990 Receptor-mediated mitogenic effect of thromboxane A2 in vascular smooth muscle cells. Biochemical Pharmacology 40 2535–2542.[CrossRef][Web of Science][Medline]
Henrion D, Dechaux E, Dowell FJ, Maclour J, Samuel JL, Lévy BI & Michel JB 1997 Alteration of flow-induced dilatation in mesenteric resistance arteries of L-NAME treated rats and its partial association with induction of cyclo-oxygenase-2. British Journal of Pharmacology 121 83–90.[Web of Science][Medline]
Hoang D, Macarthur H, Gardner A, Yang CL & Westfall TC 2003 Prostanoid-induced modulation of neuropeptide Y and noradrenaline release from the rat mesenteric bed. Autonomic and Autacoid Pharmacology 23 141–147.[CrossRef]
Holzmann S 1982 Endothelium-induced relaxation by acetylcholine associated with larger rises in cyclic GMP in coronary arterial strips. Journal of Cyclic Nucleotide Research 8 409–419.[Web of Science][Medline]
Ignarro LJ & Kadowitz PJ 1985 The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annual Review of Pharmacology and Toxicology 25 171–191.[CrossRef][Web of Science][Medline]
Jones RD, Hugh Jones T & Channer KS 2004 The influence of testosterone upon vascular reactivity. European Journal of Endocrinology 151 29–37.[Abstract]
Kawasaki H, Takasaki K, Saito A & Goto H 1988 Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat. Nature 335 164–167.[CrossRef][Medline]
Laemmel E, Bonnardel-Phu E, Hou X, Seror J & Vicaut E 2003 Interaction between nitric oxide and prostanoids in arterioles of rat cremaster muscle in vivo. American Journal of Physiology. Heart and Circulatory Physiology 285 1254–1260.
Li YJ & Duckles SP 1992 Effect of endothelium on the actions of sympathetic and sensory nerves in the perfused rat mesentery. European Journal of Pharmacology 210 23–40.[CrossRef][Web of Science][Medline]
Lissbrant IF, Lissbrant E, Persson A, Damber JE & Bergh A 2003 Endothelial cell proliferation in male reproductive organs of adult rat is high and regulated by testicular factors. Biology of Reproduction 68 1107–1111.
Liu D, Iruthayanathan M, Homan LL, Wang Y, Yang L, Wang Y & Dillon JS 2008 Dehydroepiandrosterone stimulates endothelial proliferation and angiogenesis through ERK 1/2-mediated mechanisms. Endocrinology 149 889–898.
Ma R, Wu S & Lin Q 2005 Homologous up-regulation of androgen receptor expression by androgen in vascular smooth muscle cells. Hormone Research 63 6–14.[CrossRef][Web of Science][Medline]
Marco EJ, Balfagón G, Salaíces M, Sanchez-Ferrer CF & Marín J 1985 Serotoninergic innervation of cat cerebral arteries. Brain Research 338 137–139.[CrossRef][Web of Science][Medline]
Marín J & Balfagón G 1998 Effect of clenbuterol on non-endothelial nitric oxide release in rat mesenteric arteries and the involvement of beta-adrenoceptors. British Journal of Pharmacology 124 473–478.[CrossRef][Web of Science][Medline]
Martorell A, Blanco-Rivero J, Aras-López R, Sagredo A, Balfagón G & Ferrer M 2008 Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta. Cardiovascular Research 77 590–599.
Minoves N, Balfagón G & Ferrer M 2002 Role of female sex hormones in neuronal nitric oxide release and metabolism in rat mesenteric arteries. Clinical Science 103 239–247.[Web of Science][Medline]
Miyamoto A, Hashiguchi Y, Obi T, Ishiguro S & Nishio A 2007 Ibuprofen or ozagrel increases NO release and l-nitro arginine induces TXA(2) release from cultured porcine basilar arterial endothelial cells. Vascular Pharmacology 46 85–90.[CrossRef][Web of Science][Medline]
Molderings GJ, Likungu J & Göthert M 1998 Modulation of noradrenaline release from the sympathetic nerves of human right atrial appendages by presynaptic EP3- and DP-receptors. Naunyn-Schmiedeberg's Archives of Pharmacology 358 440–444.[CrossRef][Web of Science][Medline]
Mollace V, Muscoli C, Masini E, Cuzzocrea S & Salvemini D 2005 Modulation of prostaglandin biosynthesis by nitric oxide and nitric oxide donors. Pharmacological Reviews 57 217–252.
Narumiya S, Sugimoto Y & Ushikubi F 1999 Prostanoid receptors: structures, properties, and functions. Physiological Reviews 79 1193–1226.
Ng MK 2007 New perspectives on Mars and Venus: unravelling the role of androgens in gender differences in cardiovascular biology and disease. Heart, Lung and Circulation 16 185–192.[CrossRef]
Nielsen KC & Owman C 1971 Contractile response and amine receptor mechanism in isolated middle cerebral artery of the cat. Brain Research 27 25–32.[CrossRef][Web of Science][Medline]
Nishihara M, Yokotani K, Inoue S & Osumi Y 2000 U-46619, a selective thromboxane A2 mimetic, inhibits the release of endogenous noradrenaline from the rat hippocampus in vitro. Japanese Journal of Pharmacology 82 226–231.[CrossRef][Medline]
Phillips GB, Jing TY, Resnick LM, Barbagallo M, Laragh JH & Sealey JE 1993 Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension. Journal of Hypertension 11 699–702.[CrossRef][Web of Science][Medline]
Rahmanian M & Heldin P 2002 Testicular hyaluronidase induces tubular structures of endothelial cells grown in three-dimensional collagen gel through a CD44-mediated mechanism. International Journal of Cancer 97 601–607.[CrossRef][Web of Science][Medline]
Rump LC & Schollmeyer P 1989 Effects of endogenous and synthetic prostanoids, the thromboxane A2 receptor agonist U-46619 and arachidonic acid on [3H]-noradrenaline release and vascular tone in rat isolated kidney. British Journal of Pharmacology 97 819–828.[Web of Science][Medline]
Salvemini D, Currie MG & Mollace V 1996 Nitric oxide-mediated cyclooxygenase activation. A key event in the antiplatelet effects of nitrovasodilators. Journal of Clinical Investigation 97 2562–2568.[Web of Science][Medline]
Snitsarev V, Whiteis CA, Chapleau MW & Abboud FM 2005 Neuronal prostacyclin is an autocrine regulator of arterial baroreceptor activity. Hypertension 46 540–546.
Teede HJ 2007 Sex hormones and the cardiovascular system: effects on arterial function in women. Clinical and Experimental Pharmacology and Physiology 34 672–676.[CrossRef][Web of Science][Medline]
Vanhoutte PM 1996 Endothelium-dependent responses in congestive heart failure. Journal of Molecular and Cellular Cardiology 28 2233–2240.[CrossRef][Web of Science][Medline]
Vanhoutte PM, Verbeuren JT & Clinton R 1981 Local modulation of adrenergic neuroeffector interaction in the blood vessel wall. Physiological Reviews 61 151–247.
Wang W, Brändle M & Zucker IH 1993 Indomethacin reduces acute baroreceptor resetting in the dog. Journal of Physiology 469 139–151.
Wranicz JK, Cygankiewicz I, Rosiak M, Kula P, Kula K & Zareba W 2005 The relationship between sex hormones and lipid profile in men with coronary artery disease. International Journal of Cardiology 101 105–110.[CrossRef][Web of Science][Medline]
Yamada T, Fujino T, Yuhki K, Hara A, Karibe H, Takahata O, Okada Y, Xiao CY, Takayama K, Kuriyama S et al. 2003 Thromboxane A2 regulates vascular tone via its inhibitory effect on the expression of inducible nitric oxide synthase. Circulation 108 2381–2386.
Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y & Okabe T 2007 Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochemical and Biophysical Research Communications 353 764–769.[CrossRef][Web of Science][Medline]
Zhang H, Xiao D, Longo LD & Zhang L 2006 Regulation of alpha1-adrenoceptor-mediated contractions of uterine arteries by PKC: effect of pregnancy. American Journal of Physiology. Heart and Circulatory Physiology 291 2282–2289.[CrossRef]
Received in final form 20 February 2008
Accepted 26 February 2008
Made available online as an Accepted Preprint 26 February 2008
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