Fulton, Clifford T., and John N. Stallone. Sexual dimorphism in prostanoid-potentiated vascular contraction: roles of endothelium and ovarian steroids. Am J Physiol Heart Circ Physiol 283: H2062-H2073, 2002. First published July 11, 2002 10.1152/ajpheart.00099.2002The effects of constrictor prostanoid (CP) pathway inhibitors on vascular reactivity to vasopressin (VP) and phenylephrine (PE) were examined in thoracic aortas of male, female, and ovariectomized (OVX) female Sprague-Dawley rats. Maximal contractile response of control (Cont) aortas to VP was markedly higher in females (3,885 Ϯ 332 mg/mg ring wt) than in males (810 Ϯ 148 mg). Indomethacin (Indo; 10 M) attenuated maximal response to VP in females (3,043 Ϯ 277 mg) but not in males. SQ-29,548 (SQ; 1 M) attenuated maximal response to VP in females (3,042 Ϯ 290 mg) to a similar extent as Indo. Dazoxiben (Daz; 10 M) alone had no effect, but Daz ϩ SQ attenuated maximal contractile response to VP to a similar extent as SQ alone. Removal of the endothelium in female aortas attenuated contractile responses to VP in Cont aortas. OVX attenuated maximal contractile response to VP in Cont aortas (2,093 Ϯ 329 mg) and abolished the attenuating effects of Indo. Indo, SQ, and Daz exerted identical effects on contractile responses of male, female, and OVX female aortas to PE. These findings establish the following in the rat aorta: 1) CP, probably thromboxane and/or endoperoxide, is responsible for ϳ25-30% of contractile responses of females, but not males, to VP and PE; 2) CP production by the female aorta is primarily endothelial in origin; and 3) ovarian steroids modulate production and/or actions of CP in female aortas. constrictor prostanoids; thromboxane; vasoconstriction; vascular reactivity; aortic rings; vasopressin; endoperoxide SIGNIFICANT MALE-FEMALE DIFFERENCES exist in the responses of the vasculature to vasoactive hormones, both in vivo and in vitro. There is increasing evidence that the gonadal steroid hormones play an important role in these differences through the modulation of vascular responsiveness to vasoconstrictor as well as vasodilator substances. Endothelium-derived relaxing factor [nitric oxide (NO)] and vasodilatory prostanoids (prostacyclin) are major products of the endothelium known to be involved in the modulation of local vascular function (46, 50). The presence of gonadal steroid hormone receptors in both the endothelium (12) and vascular smooth muscle (25) of blood vessels suggests that male-female differences in vascular function may involve gonadal steroid modulation of the release and/or vascular actions of NO and prostanoids.Recent studies (51, 52) have established that vasopressin (VP)-induced contractions of the rat aorta are three-to fourfold higher in females than in males, primarily due to the greater production of endothelium-derived NO in males than in females. Testosterone appears to play a primary role in the regulation of this endothelial mechanism because gonadectomy of male rats enhances contractile responses of the ao...

Contractions of rat thoracic aorta to vasopressin (VP) are threefold higher in females (F) than in males (M), primarily because nitric oxide (NO) attenuation of contraction is greater in M. To determine the role of the androgen receptor (AR) in this mechanism, vascular reactivity to VP was examined in thoracic aorta of the testicular-feminized male (Tfm) rat, which has an X-linked, recessive defect in AR function in affected M. Maximal contraction of normal aortas to VP was fourfold higher in F (4,128 +/- 291 mg/mg ring wt) than in M (971 +/- 133 mg); maximal response of Tfm (3,967 +/- 253 mg) was similar to that of normal F. N(G)-nitro-L-arginine methyl ester increased maximal response to VP threefold in M but had no effect in F or Tfm. In contrast, maximal contraction of normal aortas to phenylephrine was 43% higher in M (4,011 +/- 179 mg) than in F (2,809 +/- 78 mg); maximal response of Tfm (2,716 +/- 126 mg) was similar to that of normal F. N(G)-nitro-L-arginine methyl ester increased maximal response to phenylephrine by >50% in F and Tfm but had no effect in M. Maximal contractile response to 80 mM KCl did not differ among M, F, or Tfm. Thus androgens and normal vascular AR function are important in the greater NO-mediated attenuation of reactivity to VP in M than in F rat aorta, which may involve specific modulation of endothelial VP signal transduction pathways and NO release by androgens. These data also establish the importance of the Tfm rat as a model to study the effects of androgens on cardiovascular function.