Ponnuchamy Bharathy, Khalil Raouf A
Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1001-18. doi: 10.1152/ajpregu.90960.2008. Epub 2009 Feb 18.
The renal vasculature plays a major role in the regulation of renal blood flow and the ability of the kidney to control the plasma volume and blood pressure. Renal vascular dysfunction is associated with renal vasoconstriction, decreased renal blood flow, and consequent increase in plasma volume and has been demonstrated in several forms of hypertension (HTN), including genetic and salt-sensitive HTN. Several predisposing factors and cellular mediators have been implicated, but the relationship between their actions on the renal vasculature and the consequent effects on renal tubular function in the setting of HTN is not clearly defined. Gene mutations/defects in an ion channel, a membrane ion transporter, and/or a regulatory enzyme in the nephron and renal vasculature may be a primary cause of renal vascular dysfunction. Environmental risk factors, such as high dietary salt intake, vascular inflammation, and oxidative stress further promote renal vascular dysfunction. Renal endothelial cell dysfunction is manifested as a decrease in the release of vasodilatory mediators, such as nitric oxide, prostacyclin, and hyperpolarizing factors, and/or an increase in vasoconstrictive mediators, such as endothelin, angiotensin II, and thromboxane A(2). Also, an increase in the amount/activity of intracellular Ca(2+) concentration, protein kinase C, Rho kinase, and mitogen-activated protein kinase in vascular smooth muscle promotes renal vasoconstriction. Matrix metalloproteinases and their inhibitors could also modify the composition of the extracellular matrix and lead to renal vascular remodeling. Synergistic interactions between the genetic and environmental risk factors on the cellular mediators of renal vascular dysfunction cause persistent renal vasoconstriction, increased renal vascular resistance, and decreased renal blood flow, and, consequently, lead to a disturbance in the renal control mechanisms of water and electrolyte balance, increased plasma volume, and HTN. Targeting the underlying genetic defects, environmental risk factors, and the aberrant renal vascular mediators involved should provide complementary strategies in the management of HTN.
肾血管系统在调节肾血流量以及肾脏控制血浆容量和血压的能力方面发挥着主要作用。肾血管功能障碍与肾血管收缩、肾血流量减少以及血浆容量随之增加有关，并且已在多种形式的高血压（HTN）中得到证实，包括遗传性高血压和盐敏感性高血压。虽然已经涉及到一些易感因素和细胞介质，但在高血压情况下，它们对肾血管系统的作用与对肾小管功能的后续影响之间的关系尚未明确界定。肾单位和肾血管系统中离子通道、膜离子转运体和/或调节酶的基因突变/缺陷可能是肾血管功能障碍的主要原因。环境风险因素，如高盐饮食、血管炎症和氧化应激，会进一步促进肾血管功能障碍。肾内皮细胞功能障碍表现为血管舒张介质（如一氧化氮、前列环素和超极化因子）释放减少，和/或血管收缩介质（如内皮素、血管紧张素II和血栓素A2）增加。此外，血管平滑肌细胞内钙离子浓度、蛋白激酶C、Rho激酶和丝裂原活化蛋白激酶的量/活性增加会促进肾血管收缩。基质金属蛋白酶及其抑制剂也可能改变细胞外基质的组成并导致肾血管重塑。肾血管功能障碍的细胞介质上遗传和环境风险因素之间的协同相互作用会导致持续性肾血管收缩、肾血管阻力增加和肾血流量减少，进而导致水和电解质平衡的肾脏控制机制紊乱、血浆容量增加和高血压。针对潜在的遗传缺陷、环境风险因素以及所涉及的异常肾血管介质应能为高血压的管理提供补充策略。
