title: Sex differences in nitric oxide-mediated attenuation of vascular reactivity to vasopressin are abolished by gonadectomy.
abstract: In the rat thoracic aorta, contractile responses to vasopressin are two-fold higher in females than in males, primarily because nitric oxide-mediated attenuation of contraction is greater in males than in females. To determine the role of the gonadal steroids in this phenomenon, the effects of gonadectomy on nitric oxide and vascular reactivity to vasopressin were examined in thoracic aortae of age-matched intact and gonadectomized male and female rats. Maximal response to vasopressin was markedly higher in gonadectomized-male than in intact-male aortae (2729 +/- 421 vs. 1375 +/- 222 mg/mg ring weight; P < 0.01). Inhibition of nitric oxide synthase with NG-methyl-L-arginine (L-NMMA, 250 microM) enhanced maximal response of intact-male (2824 +/- 413 mg/mg ring weight; P < 0.01) but not gonadectomized-male aortae (3034 +/- 365 mg/mg ring weight; P > 0.05). Sensitivity of male aortae to vasopressin was unaffected by gonadectomy or L-NMMA. Maximal contraction to vasopressin did not differ between gonadectomized-female and intact-female aortae (4003 +/- 180 vs. 4645 +/- 212 mg/mg ring weight; P > 0.05). L-NMMA increased the sensitivity but not the maximal response to vasopressin in intact-female and gonadectomized-female aortae. In contrast, maximal response to phenylephrine was similar in gonadectomized-male and intact-male aortae (3843 +/- 175 vs. 4234 +/- 206 mg/mg ring weight; P > 0.05); L-NMMA enhanced maximal tension more in gonadectomized-male than in intact male aortae (4645 +/- 206 vs. 4612 +/- 176 mg/mg ring weight). Maximal contraction to phenylephrine was substantially higher in gonadectomized-female than in intact-female aortae (4303 +/- 104 vs. 3341 +/- 155 mg/mg ring weight; P < 0.001); L-NMMA enhanced maximal tension more in intact-female than in gonadectomized-female aortae (5073 +/- 158 vs. 4788 +/- 140 mg/mg ring weight). These results strongly suggest that the gonadal steroids exert important regulatory effects on nitric oxide release in the rat aorta, which are vasoconstrictor-specific and appear to involve basal and/or agonist-stimulated nitric oxide release.
authors.affiliation: Department of Physiology, Northeastern Ohio Universities College of Medicine, Rootstown 44272.
authors.forename: J N
authors.initials: JN
authors.lastname: Stallone
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009919:Orchiectomy; D010052:Ovariectomy; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014667:Vasopressins / Q000494:pharmacology*; D019323:omega-N-Methylarginine
chemical_list: D014667:Vasopressins; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D011189:Potassium Chloride; D001120:Arginine; D000109:Acetylcholine