G-PROTEIN ALTERATIONS IN HYPERTENSION AND AGING
G-PROTEIN ALTERATIONS IN HYPERTENSION AND AGING
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DOI：
10.1161/01.hyp.26.5.725
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发表时间：
1995-11-01
期刊：
影响因子：
8.3
通讯作者：
CHORAZYCZEWSKI, J
中科院分区：
文献类型：
--
作者：
FELDMAN, RD;TAN, CM;CHORAZYCZEWSKI, J
血管舒张功能缺陷在高血压状态的发病机制和/或维持以及老年人高血压的易感性中可能是重要的。β-肾上腺素能介导的血管舒张功能受损和淋巴细胞β-肾上腺素能腺苷酸环化酶激活减少已在衰老和高血压中得到证实。负责这些变化的细胞机制仍不清楚。为了确定这些缺陷是否可能是由于鸟嘌呤核苷酸调节蛋白的改变（G蛋白）连接受体活化与效应功能，我们评估（1）人淋巴细胞腺苷酸环化酶活性，（2）通过霍乱毒素介导的[P-32]ADP核糖基化刺激G蛋白，并在高血压受试者中，用α（s）特异性和β亚基抗血清，和（3）通过百日咳毒素介导的[P-32]ADP核糖基化抑制G蛋白，在老年受试者中，用α（11，2）-和β-亚单位特异性抗血清。来自老年受试者和高血压受试者的淋巴细胞表现出相当的异丙肾上腺素刺激的腺苷酸环化酶的减少。然而，氟化铝刺激的活性降低，仅在淋巴细胞高血压受试者。此外，氟化铝刺激的活动与平均动脉压呈负相关。在年轻的高血压受试者的淋巴细胞，霍乱毒素介导的标记显着减少，然而，刺激G蛋白标记的免疫检测是不变的。在老年受试者的淋巴细胞中，霍乱毒素介导的标记没有改变，但是，百日咳毒素介导的标记显着增加。与此相反，抑制性G蛋白标记的免疫检测是不变的。总的来说，这项研究表明G蛋白功能在高血压和衰老中的改变。在这两种情况下，腺苷酸环化酶的刺激受损。然而，这些缺陷与刺激性和抑制性G蛋白的不同改变有关。
Defective vasodilator function could be important in the pathogenesis and/or maintenance of the hypertensive state and the predisposition of the elderly to hypertension. Impaired beta-adrenergic-mediated vasodilation and reduced lymphocyte beta-adrenergic activation of adenyl cyclase have been demonstrated both in aging and with hypertension. The cellular mechanisms responsible for these alterations remain unclear. To determine if these defects may be due to alterations in guanine nucleotide regulatory proteins (G proteins) that link receptor activation with effector function, we assessed (1) human lymphocyte adenyl cyclase activity, (2) stimulatory G proteins by cholera toxin-mediated [P-32]ADP ribosylation and, in hypertensive subjects, with alpha(s)-specific and beta-subunit antisera, and (3) inhibitory G proteins by pertussis toxin-mediated [P-32]ADP ribosylation and, in older subjects, with alpha(11,2)- and beta-subunit-specific antisera. Lymphocytes from older subjects and from hypertensive subjects demonstrated a comparable reduction in isoproterenol-stimulated adenyl cyclase. However, aluminum fluoride-stimulated activity was reduced only in lymphocytes from hypertensive subjects. Furthermore, aluminum fluoride-stimulated activity was inversely correlated with mean arterial pressure. In lymphocytes from younger hypertensive subjects, cholera toxin-mediated labeling was significantly reduced; however, stimulatory G protein labeling by immunodetection was unaltered. In lymphocytes from older subjects, cholera toxin-mediated labeling was not altered; however, pertussis toxin-mediated labeling was significantly increased. In contrast, inhibitory G protein labeling by immunodetection was unaltered. Overall, the study suggests alterations of G protein function in hypertension and aging. In both conditions, stimulation of adenyl cyclase is impaired. However, these defects are associated with divergent alterations in stimulatory and inhibitory G proteins.