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

为阐明肾心钠素受体的特性及其在血压调节中的作用，我们用~（125）I标记的心钠素对大鼠肾细胞膜进行了放射性标记受体分析（RRA），并在冰冻切片上进行了体外放射自显影（ARG）。自发性高血压大鼠（SHR）肾内~（125）I标记ANP密度在3-4、5-7和12-15周龄组均低于对照组，提示SHR在遗传上具有较少的结合位点。在12周龄的SHR中，观察到用抗高血压利尿剂吲达帕胺治疗后ANP结合位点的数量减少。DOCA盐性高血压大鼠血浆ANP浓度显著升高，肾脏ANP受体密度降低。这些结果表明，在该模型中，ANP受体活性随血压升高而下调。我们还检测了肾活检标本肾小球中的ANP结合位点，尽管患者发病率与肾脏中ANP程度之间的关系尚未确定。本文研究了高血压和高血压前期SHR肾脏α肾上腺素能受体的差异，并与心钠素受体进行了比较。通过计算机分析[~ 3 H-布那唑嗪]和[~ 3 H-育亨宾]的体外巨量ARG，发现高血压前期SHR的α_1和α_2肾上腺素能受体均增多，提示ANP在高血压状态的控制和进展中起重要作用。

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.