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Change of atrial natriuretic polypeptide receptors in the hypertensive state and the effect of drugs on these receptors.

高血压状态下心房钠尿多肽受体的变化及药物对这些受体的影响。

基本信息

批准号：
61480209
负责人：
OTA Zensuke
金额：
$ 4.03万
依托单位：
Okayama University,
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

To elucidate the characteristics of renal receptors for atrial natriuretic polypeptide(ANP) and their role in the regulation of blood pressure, we performed radiolabeled receptor assay(RRA) on rat renal membrane fractions and in vitro autoradiography (ARG) on frozen sections using 125I-labeled ANP. The density of 125I-labeled ANP in the kidneys of spontaneously hypertensive rats(SHR) was lower in all age groups(3-4, 5-7 and 12-15 weeks) than of control rats, suggesting that SHR have fewer binding sites genetically. A decrease in the number of ANP binding sites in 12 week-old SHR was observed following treatment with the anti-hypertensive diuretic indapamide. In DOCA salt hypertensive rats, plasma concentration of ANP was increased remarkably and the density of ANP receptors in the kidney was decreased. These result suggest that in this model ANP receptor activity was down regulated with increasing blood pressure. We also detected the ANP binding sites in the glomerulus of renal biopsy specimens, although a relationship between patients morbidity and the degree of ANP in the kidney was not determined. Differences of alpha adrenergic receptors in the kidneys of hypertensive and prehypertensive SHR were investigated and compared with those for ANP receptors. Both alpha1 and alpha2 adrenoceptors were more numerous in pre-hypertensive SHR as determined by computerized analysis of in vitro macro ARG of [3H -bunazosin and [3H -yohimbine.We concluded that ANP play an important role in the control and progression of the hypertensive state.

为了阐明心房利钠多肽（ANP）肾受体的特征及其在血压调节中的作用，我们对大鼠肾膜部分进行了放射性标记受体测定（RRA），并用125i标记的ANP对冷冻切片进行了体外放射自显影（ARG）。自发性高血压大鼠（SHR）肾脏中125i标记ANP的密度在所有年龄组（3-4周、5-7周和12-15周）均低于对照组，提示SHR的结合位点较少。在降压利尿剂吲达帕胺治疗后，观察到12周大SHR中ANP结合位点数量减少。DOCA盐高血压大鼠血浆ANP浓度显著升高，肾内ANP受体密度降低。这些结果表明，在该模型中ANP受体活性随着血压升高而下调。我们还在肾活检标本的肾小球中检测到ANP结合位点，尽管患者发病率与肾脏ANP程度之间的关系尚未确定。研究高血压和高血压前期SHR患者肾脏α -肾上腺素能受体与ANP受体的差异。通过计算机分析[3H -布那佐辛和[3H -育亨宾的体外宏观ARG，可以确定高血压前期SHR中α 1和α 2肾上腺素受体的数量更多。我们认为ANP在高血压状态的控制和进展中起重要作用。