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一氧化氮介导的血管对血管加压素反应性减弱中的性别差异会因性腺切除术而消除。

Sex differences in nitric oxide-mediated attenuation of vascular reactivity to vasopressin are abolished by gonadectomy.

作者信息

Stallone J N

机构信息

Department of Physiology, Northeastern Ohio Universities College of Medicine, Rootstown 44272.

出版信息

Eur J Pharmacol. 1994 Jul 11;259(3):273-83. doi: 10.1016/0014-2999(94)90654-8.

DOI:10.1016/0014-2999(94)90654-8
PMID:7982454
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.

摘要

在大鼠胸主动脉中,雌性对血管加压素的收缩反应比雄性高两倍,主要原因是一氧化氮介导的收缩减弱在雄性中比在雌性中更明显。为了确定性腺类固醇在这一现象中的作用,研究了去势对年龄匹配的完整和去势雄性及雌性大鼠胸主动脉中一氧化氮和血管对血管加压素反应性的影响。去势雄性大鼠胸主动脉对血管加压素的最大反应明显高于完整雄性大鼠(2729±421对1375±222毫克/毫克环重;P<0.01)。用NG-甲基-L-精氨酸(L-NMMA,250微摩尔)抑制一氧化氮合酶可增强完整雄性大鼠胸主动脉的最大反应(2824±413毫克/毫克环重;P<0.01),但对去势雄性大鼠胸主动脉无增强作用(3034±365毫克/毫克环重;P>0.05)。雄性大鼠胸主动脉对血管加压素的敏感性不受去势或L-NMMA的影响。去势雌性大鼠和完整雌性大鼠胸主动脉对血管加压素的最大收缩无差异(4003±180对4645±212毫克/毫克环重;P>0.05)。L-NMMA增加了完整雌性和去势雌性大鼠胸主动脉对血管加压素的敏感性,但未增加最大反应。相反,去势雄性大鼠和完整雄性大鼠胸主动脉对去氧肾上腺素的最大反应相似(3843±175对4234±206毫克/毫克环重;P>0.05);L-NMMA对去势雄性大鼠胸主动脉最大张力的增强作用比对完整雄性大鼠胸主动脉更明显(4645±206对4612±176毫克/毫克环重)。去势雌性大鼠胸主动脉对去氧肾上腺素的最大收缩明显高于完整雌性大鼠(4303±104对3341±155毫克/毫克环重;P<0.001);L-NMMA对完整雌性大鼠胸主动脉最大张力的增强作用比对去势雌性大鼠胸主动脉更明显(5073±158对4788±140毫克/毫克环重)。这些结果强烈表明,性腺类固醇对大鼠主动脉中一氧化氮的释放具有重要的调节作用,这种作用具有血管收缩剂特异性,似乎涉及基础和/或激动剂刺激的一氧化氮释放。

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