Department of Pharmacology, Universidade Federal do Paraná, Curitiba, PR, Brazil; Department of Physiology, Georgia Health Sciences University, Augusta, GA, USA.
Institute of Biological Sciences, Medical and Health, Universidade Paranaense, Umuarama, PR, Brazil.
Vascul Pharmacol. 2014 Feb;60(2):67-74. doi: 10.1016/j.vph.2013.12.001. Epub 2013 Dec 7.
A high salt diet is associated with reduced activity of the renin-angiotensin-aldosterone system (RAAS). However, normotensive rats exposed to high sodium do not show changes in systemic arterial pressure. We hypothesized that, despite the reduced circulating amounts of angiotensin II induced by a high salt diet, the cardiovascular system's reactivity to angiotensin II is increased in vivo, contributing to maintain arterial pressure at normal levels. Male Wistar rats received chow containing 0.27% (control), 2%, 4%, or 8% NaCl for six weeks. The high-sodium diet did not lead to changes in arterial pressure, although plasma levels of angiotensin II and aldosterone were reduced in the 4% and 8% NaCl groups. The 4% and 8% NaCl groups showed enhanced pressor responses to angiotensin I and II, accompanied by unchanged and increased angiotensin-converting enzyme activity, respectively. The 4% NaCl group showed increased expression of angiotensin II type 1 receptors and reduced expression of angiotensin II type 2 receptors in the aorta. In addition, the hypotensive effect of losartan was reduced in both 4% and 8% NaCl groups. In conclusion these results explain, at least in part, why the systemic arterial pressure is maintained at normal levels in non-salt sensitive and healthy rats exposed to a high salt diet, when the functionality of RAAS appears to be blunted, as well as suggest that angiotensin II has a crucial role in the vascular dysfunction associated with high salt intake, even in the absence of hypertension.
高盐饮食与肾素-血管紧张素-醛固酮系统(RAAS)活性降低有关。然而,暴露于高钠的正常血压大鼠的系统动脉压没有变化。我们假设,尽管高盐饮食导致循环中血管紧张素 II 的量减少,但血管紧张素 II 在体内的心血管系统反应性增加,有助于将动脉压维持在正常水平。雄性 Wistar 大鼠接受含 0.27%(对照)、2%、4%或 8% NaCl 的饮食 6 周。高盐饮食并未导致动脉压变化,尽管 4%和 8% NaCl 组的血浆血管紧张素 II 和醛固酮水平降低。4%和 8% NaCl 组对血管紧张素 I 和 II 的加压反应增强,分别伴有不变和增加的血管紧张素转换酶活性。4% NaCl 组在主动脉中显示出血管紧张素 II 型 1 受体表达增加和血管紧张素 II 型 2 受体表达减少。此外,在 4%和 8% NaCl 组中,氯沙坦的降压作用降低。总之,这些结果至少部分解释了为什么在暴露于高盐饮食的非盐敏感和健康大鼠中,尽管 RAAS 的功能似乎减弱,但系统动脉压仍维持在正常水平,并且表明血管紧张素 II 在高盐摄入相关的血管功能障碍中具有关键作用,即使在没有高血压的情况下也是如此。