NEUROHYPOPHYSIAL POLYPEPTIDES AND RENAL PROSTAGLANDINS

精氨酸-加压素（AVP）和其他血管活性肽， 血管紧张素II和缓激肽刺激肾血管紧张素（PGs） 合成. 有证据表明，肾PG作为负反馈 调节剂对抗糖尿病诱导的抗利尿和血管收缩。 AVP刺激PG的作用是否与其自身的作用有关尚不清楚。 抗利尿或血管加压活性。 我们已经证明某些类似物 加压素和催产素，它们缺乏抗利尿剂， 血管加压活性刺激钠和水的肾排泄。 它 这些肽的利尿钠作用可能是 通过肾脏PG释放介导。 因此，神经垂体肽可能， 具有PG刺激活性，不依赖于其抗利尿剂，或 血管加压活性 我们将研究PG刺激活性的 这些肽在大鼠中，并检查其与升压的关系， 该分子的抗利尿和利钠活性。 我们还将 研究这些肽对肾脏磷脂酶活性的影响， 切片和肾微粒体环氧合酶活性，目的是 确定其作用部位和机制。 放射化学方法和 将采用放射免疫测定法（RIA）测定PG。 我们的长期目标是生产特定的肾脏PG释放肽。 肾PG调节肾循环，并且还可以作为生理调节剂起作用。 降压机制 特异性肾PG释放肽可能 代表了一类可能具有治疗潜力的新型药物 肾血管疾病和高血压疾病。

Arginine-vasopressin (AVP) and other vasoactive peptides such as angiotensin II and bradykinin stimulate renal prostaglandins (PGs) synthesis. There is evidence that renal PGs serve as negative feedback modulators opposing the hormone-induced antidiuresis and vasoconstriction. It is not known whether the PG-stimulating effect of AVP is related to its antidiuretic or vasopressor activity. We have shown that certain analogs of vasopressin and oxytocin which are devoid of antidiuretic and vasopressor activities stimulate renal excretion of sodium and water. It is possible that the natriuretic-diuretic action of these peptides is mediated via renal PG release. Neurohypophysial peptides may, therefore, have PG-stimulating activity, independent of their antidiuretic or vasopressor activity. We will investigate the PG-stimulating activity of these peptides in rats and examine its relationship to the pressor, antidiuretic and natriuretic activities of the molecule. We will also study the effects of these peptides on the phospholipase activity in renal slices and on the renal microsomal cyclooxygenase activity with the aim to define their site and mechanism of action. Radiochemical methods and radioimmunoassays (RIAs) will be employed for the determination of PGs. Our long-term goal is to produce specific renal PG-releasing peptides. Renal PGs modulate renal circulation and may also function as a physiologic antihypertensive mechanism. Specific renal PG-releasing peptides may represent a novel class of drugs that may have potential for the treatment of renovascular and hypertensive diseases.