Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared with men.
Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous microvasculature of premenopausal women compared with men.
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与男性相比，绝经前女性皮肤微血管的血管紧张素 II 2 型受体介导的扩张更大。
DOI：
10.1152/japplphysiol.00382.2023
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Stanhewicz,AnnaE
中科院分区：
文献类型：
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作者：
Schwartz,KelseyS;Lang,JamesA;Stanhewicz,AnnaE
与年龄相匹配的男性相比，绝经前女性的肾素-血管紧张素系统（RAS）的不同激活可能导致心血管结局的性别差异。与男性相比，女性表现出血管收缩剂血管紧张素II 1型受体（AT 1 R）的活化减少，有证据表明，女性也可能具有血管舒张剂血管紧张素II 2型受体（AT 2 R）的敏感性增加。然而，很少有体内研究直接检查AT 2 R介导的扩张的性别差异，或AT 1 R和AT 2 R介导的血管反应之间的平衡。使用皮肤微循环作为模型，我们假设，AT 2 R介导的扩张将在绝经前女性比男性更大，AT 1 R阻断将增加AT 2 R介导的扩张在更大程度上在男性比女性。12名健康女性（22 ± 3岁）和12名男性（23 ± 5岁）将两根皮内微透析纤维置于前臂腹侧，在对照纤维部位和43 µM氯沙坦（AT 1 R拮抗剂）治疗部位进行化合物21（AT 2 R激动剂; 10− 12至10− 8 M）的分级输注。通过激光多普勒血流仪连续测量红细胞流量，并将皮肤血管电导[CVC =流量/平均动脉压（MAP）]标准化为最大值[%max; 28 mM硝普钠（SNP）+43 °C]。女性AT 2 R介导的血管扩张大于男性（女性：25 ± 4% vs.男性：15 ± 2%max，P = 0.03）。局部AT 1 R抑制可增加男性AT 2 R介导的血管舒张（氯沙坦：26 ± 4% vs对照组：15 ± 2%max，P < 0.001），但对女性无影响（氯沙坦：27 ± 6% vs对照组：25 ± 4%max，P> 0.05）。这些数据表明，绝经前妇女有一个更大的AT 2 R介导的血管舒张反应比男性，和AT 1 R激活抑制AT 2 R介导的扩张在男性，但不是在women.NEW &值得注意的是，绝经前妇女有更大的保护心血管疾病比年龄匹配的男性。然而，血管收缩性血管紧张素II 1型受体（AT 1 R）和血管舒张性血管紧张素II 2型受体（AT 2 R）在介导这些性别差异中的作用尚不清楚。在这里，我们证明，女性有更大的AT 2 R介导的血管舒张比男性和AT 1 R否定AT 2 R介导的扩张在男性，但不是在女性。
Differential activation of the renin-angiotensin system (RAS) likely contributes to sex differences in cardiovascular outcomes in premenopausal women compared with age-matched men. Women demonstrate reduced activation of the vasoconstrictor angiotensin II type 1 receptors (AT1R) compared with men, and evidence suggests that women also likely have increased sensitivity of the vasodilatory angiotensin II type 2 receptors (AT2R). However, few in vivo studies have directly examined sex differences in AT2R-mediated dilation, or the balance between AT1R- and AT2R-mediated vascular responses in humans. Using the cutaneous microcirculation as a model, we hypothesized that AT2R-mediated dilation would be greater in premenopausal women compared with men, and that AT1R-blockade would augment AT2R-mediated dilation to a greater extent in men than in women. Twelve healthy women (22 ± 3 yr) and 12 men (23 ± 5 yr) had two intradermal microdialysis fibers placed in the ventral forearm for graded infusions of compound 21 (AT2R agonist; 10−12to 10−8M) in a control fiber site and a site treated with 43 µM losartan (AT1R antagonist). Red blood cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance [CVC = flux/mean arterial pressure (MAP)] was normalized to maximum [%max; 28 mM sodium nitroprusside (SNP) + 43 °C]. Women had greater AT2R-mediated dilation compared with men (women: 25 ± 4 vs. men: 15 ± 2%max,P= 0.03). Local AT1R inhibition increased AT2R-mediated dilation in men (losartan: 26 ± 4 vs. control: 15 ± 2%max,P< 0.001) but had no effect in women (losartan: 27 ± 6 vs. control: 25 ± 4%max,P> 0.05). These data suggest that premenopausal women have a greater AT2R-mediated vasodilation response than men, and that AT1R activation inhibits AT2R-mediated dilation in men, but not in women.NEW & NOTEWORTHYPremenopausal women have greater protection against cardiovascular disease than age-matched men. However, the role of vasoconstrictor angiotensin II type 1 receptors (AT1R) and vasodilatory angiotensin II type 2 receptors (AT2R) in mediating these sex differences is unclear. Here, we demonstrate that women have greater AT2R-mediated vasodilation than men and that AT1R negates AT2R-mediated dilation in men, but not in women.