NEUROHYPOPHYSIAL POLYPEPTIDES AND RENAL PROSTAGLANDINS

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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.