Angiotensinogen genotype predicts abnormal renal hemodynamics in young hypertensive patients
Angiotensinogen genotype predicts abnormal renal hemodynamics in young hypertensive patients
复制标题
DOI：
10.1097/hjh.0b013e3282ffb417
复制
发表时间：
2008-07-01
影响因子：
4.9
通讯作者：
Fisher, Naomi Deirdre L.
中科院分区：
文献类型：
--
作者：
Patel, Tejas V.;Williams, Gordon H.;Fisher, Naomi Deirdre L.
目的原发性高血压患者肾脏血浆对血管紧张素II的反应性降低提示肾脏血管紧张素II的病理性增加。这种钝化与血管紧张素原235 TT基因型有关。作为几个措施的肾功能随着年龄的增长而下降，我们试图确定年龄和基因型的相互作用，这个中间phenotype.Design和方法315名参与者有肾血浆流量反应降压剂量的血管紧张素II（3纳克/公斤/分钟）测量对氨基马尿酸清除率高钠平衡。根据平均年龄将个体分为年轻组（<45岁）和老年组（>= 45岁）。一个子集的参与者也研究了captopripl.Results管理后，年龄，基线肾血浆流量，BMI和血管紧张素原235基因型独立预测肾血浆流量反应血管紧张素II。老年人的肾血浆流量反应低于年轻人（P=0.03，高血压患者; P=0.004，血压正常者）。高血压患者和血压正常个体携带血管紧张素原235 MM或MT基因型均显示这种负相关（P=0.005，高血压患者; P=0.05，血压正常个体）。然而，在血管紧张素原235 TT纯合子的模式不同：血压正常的人有下降，肾血管反应性随年龄的增长（P=0.01），但高血压患者没有（P=0.72）。年轻的高血压患者已经表现出迟钝的反应。在所有基因亚型中，只有血管紧张素原235 TT变异型高血压患者在服用开搏通后肾血管对血管紧张素II的反应性增强（P=0.03）。这种异常反应可通过血管紧张素转换酶抑制来纠正。年龄和基因型相互作用的首次报道可能对原发性高血压的分析和管理具有重要意义。
Objective In essential hypertensive patients, blunted renal plasma flow responsiveness to angiotensin II suggests a pathologic increase in angiotensin II in the kidneys. This blunting has been associated with the angiotensinogen 235TT genotype. As several measures of renal function decline with age, we sought to determine the interaction of age and genotype on this intermediate phenotype.Design and methods Three hundred fifteen participants had renal plasma flow response to subpressor doses of angiotensin II (3 ng/kg/min) measured by para-aminohippuric acid clearance in high-sodium balance. Individuals were divided by median age into young (< 45years) and older(>= 45years) sets. A subset of participants was also studied after administration of captopril.Results Age, baseline renal plasma flow, BMI and angiotensinogen 235 genotype independently predicted renal plasma flow responsiveness to angiotensin II. Renal plasma flow responses were lower in older individuals than younger (P=0.03, hypertensive patients; P=0.004, normotensive individuals). Both hypertensive patients and normotensive individuals carrying either angiotensinogen 235MM or MT genotypes showed this inverse association (P=0.005, hypertensive patients; P=0.05, normotensive individuals). However, among angiotensinogen 235TT homozygotes the pattern differed: normotensive individuals had a fall in renal vascular responsiveness with age (P=0.01) but hypertensive patients did not (P=0.72). Young hypertensive patients already showed blunted responses. Of all genotype subsets, only angiotensinogen 235TT hypertensive patients showed enhancement (P=0.03) of the renal vascular responsiveness to angiotensin II after captopril.Conclusion The angiotensinogen 235TT variant predicts premature blunting of renal vascular responsiveness among young hypertensive patients. This abnormal response is corrected by angiotensin-converting enzyme inhibition. This first report of age and genotype interaction may have important implications in the profiling and management of essential hypertension.