Sex-specific long-term blood pressure regulation: Modeling and analysis
Sex-specific long-term blood pressure regulation: Modeling and analysis
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DOI：
10.1016/j.compbiomed.2018.11.002
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发表时间：
2019-01-01
影响因子：
7.7
通讯作者：
Layton, Anita T.
中科院分区：
文献类型：
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作者：
Leete, Jessica;Layton, Anita T.
高血压是一项全球性健康挑战：它影响着全世界 10 亿人，据估计占所有心血管疾病病例或类型的 60% 以上。部分原因是血压调节机制的性别差异尚未得到充分了解，尽管女性的依从性和治疗率普遍较高，但与男性相比，实现血压控制的女性高血压患者较少。因此，本研究的目的是确定哪些因素导致针对肾素血管紧张素系统（RAS）的抗高血压治疗产生性别二态性。为了实现这一目标，我们开发了特定性别的血压调节模型。显示了 RAS、基线肾上腺素水平和肾交感神经活动 (RSNA) 反应性的性别差异。该模型的一个新颖之处是结合的血管紧张素 II 2 型受体（AT2R 结合的 Ang II）对肾血管阻力的性别特异性血管舒张作用的表现。模型模拟表明，RSNA 的性别差异是女性抵抗高血压的最大原因，因为 RSNA 对传入小动脉阻力有直接影响。此外，该模型预测，与血管紧张素转换酶抑制剂相比，AT2R 结合的 Ang II 对肾血管阻力的性别特异性血管舒张作用可能解释了血管紧张素受体阻滞剂在治疗女性高血压（而非男性）方面具有更高的有效性。
Hypertension is a global health challenge: it affects one billion people worldwide and is estimated to account for >60% of all cases or types of cardiovascular disease. In part because sex differences in blood pressure regulation mechanisms are not sufficiently well understood, fewer hypertensive women achieve blood pressure control compared to men, even though compliance and treatment rates are generally higher in women. Thus, the objective of this study is to identify which factors contribute to the sexual dimorphism in response to anti-hypertensive therapies targeting the renin angiotensin system (RAS). To accomplish that goal, we develop sex specific blood pressure regulation models. Sex differences in the RAS, baseline adosterone level, and the reactivity of renal sympathetic nervous activity (RSNA) are represented. A novel aspect of the model is the representation of sex-specific vasodilatory effect of the bound angiotensin II type two receptor (AT2R-bound Ang II) on renal vascular resistance. Model simulations suggest that sex differences in RSNA are the largest cause of female resistance to developing hypertension due to the direct influence of RSNA on afferent arteriole resistance. Furthermore, the model predicts that the sex-specific vasodilatory effects of AT2R-bound Ang II on renal vascular resistance may explain the higher effectiveness of angiotensin receptor blockers in treating hypertensive women (but not men), compared to angiotensin converting enzyme inhibitors.