Sex Differences in the Pressor and Tubuloglomerular Feedback Response to Angiotensin II
Sex Differences in the Pressor and Tubuloglomerular Feedback Response to Angiotensin II
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DOI：
10.1161/hypertensionaha.111.178715
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发表时间：
2012-01-01
期刊：
影响因子：
8.3
通讯作者：
Denton, Kate M.
中科院分区：
文献类型：
--
作者：
Brown, Russell D.;Hilliard, Lucinda M.;Denton, Kate M.
人们对心血管疾病病理学中性别差异的认识正在不断增强。此前，我们已经证明了 2 型血管紧张素受体 (AT(2)R) 在对 Ang II 的动脉压反应中的性别差异中发挥的作用。肾小球反馈 (TGF) 有助于设定压力尿钠特性，其反应性与肾脏 Ang II 水平密切相关。我们假设，在女性中，对 Ang II 的升压反应减弱是通过增强的 AT(2)R 机制介导的，该机制部分抵消了 Ang II 诱导的 TGF 机制的敏化。通过遥测技术测量接受 Ang II（600 ng/kg/分钟 SC）的雄性和雌性野生型 (WT) 和 AT(2)R 敲除 (AT(2)R-KO) 小鼠的平均动脉压。 4 组之间的基础 24 小时平均动脉压没有差异。 Ang II输注10天后，雄性WT (28 +/- 6 mm Hg)、雄性AT(2)R-KO (26 +/- 2 mm Hg)和雌性AT(2)R-KO (26 +/- 4 mm Hg)小鼠的平均动脉压增加，然而，雌性WT小鼠的反应减弱(12 +/- 4 mm Hg；性别和基因型之间的P = 0.016）。在急性血管紧张素II抑制物输注（100ng/kg每分钟IV）之前和期间测定TGF特征。基础 TGF 反应在各组之间没有差异。在雄性 WT、雄性 AT(2)R-KO 和雌性 AT(2)R-KO 小鼠中观察到了响应 Ang II 的停流压力最大变化的预期增加和 TGF 敏感性的增强，但在雌性 WT 小鼠中没有观察到（性别和基因型之间的 P < 0.05；两者）。总之，这些数据表明，增强的 AT(2)R 介导途径可抵消 Ang II 的高血压作用，并减弱女性中 Ang II 依赖性的 TGF 活性重置。因此，AT(2)R 的增强可能部分是绝经前妇女对抗心血管疾病的保护作用的基础。 （高血压。2012；59：129-135。）。在线数据补充
Awareness of sex differences in the pathology of cardiovascular disease is increasing. Previously, we have shown a role for the angiotensin type 2 receptor (AT(2)R) in the sex differences in the arterial pressure response to Ang II. Tubuloglomerular feedback (TGF) contributes in setting pressure-natriuresis properties, and its responsiveness is closely coupled to renal Ang II levels. We hypothesize that, in females, the attenuated pressor response to Ang II is mediated via an enhanced AT(2)R mechanism that, in part, offsets Ang II-induced sensitization of the TGF mechanism. Mean arterial pressure was measured via telemetry in male and female wild-type (WT) and AT(2)R knockout (AT(2)R-KO) mice receiving Ang II (600 ng/kg per minute SC). Basal 24-hour mean arterial pressure did not differ among the 4 groups. After 10 days of Ang II infusion, mean arterial pressure increased in the male WT (28 +/- 6 mm Hg), male AT(2)R-KO (26 +/- 2 mm Hg), and female AT(2)R-KO (26 +/- 4 mm Hg) mice, however, the response was attenuated in female WT mice (12 +/- 4 mm Hg; P between sex and genotype = 0.016). TGF characteristics were determined before and during acute subpressor Ang II infusion (100 ng/kg per minute IV). Basal TGF responses did not differ between groups. The expected increase in maximal change in stop-flow pressure and enhancement of TGF sensitivity in response to Ang II was observed in the male WT, male AT(2)R-KO, and female AT(2)R-KO but not in the female WT mice (P between sex and genotype < 0.05; both). In conclusion, these data indicate that an enhanced AT(2)R-mediated pathway counterbalances the hypertensive effects of Ang II and attenuates the Ang II-dependent resetting of TGF activity in females. Thus, the enhancement of the AT(2)R may, in part, underlie the protection that premenopausal women demonstrate against cardiovascular disease. (Hypertension. 2012;59:129-135.). Online Data Supplement