NATRIURETIC, DIURETIC AND ANTI-ARGININE-VASOPRESSIN (ADH) EFFECTS OF TWO ANALOGS OF OXYTOCIN: [4-LEUCINE]-OXYTOCIN AND [2,4-DIISOLEUCINE]-OXYTOCIN

¹ Department of Pharmacology, Cornell University Medical College, New York, New York and Department of Chemistry, Cornell University, Ithaca, New York

[4-Leucine]-oxytocin and [2,4-diisoleucine]-oxytocin were found to have a potent natriuretic-diuretic effect in rats during both water diuresis and vasopressin antidiuresis. Potassium excretion was only slightly increased. Changes in free-water clearance suggest that the peptides induce natriuresis and diuresis by inhibiting sodium reabsorption at the proximal tubule. [4-Leucine]-oxytocin has a stronger natriuretic activity than that of [2,4-diisoleucine]-oxytocin. [4-Leucine]-oxytocin was also found to inhibit the antidiuretic response to arginine-vasopressin. At effective dose level, it completely antagonized the vasopressin antidiuresis in water-loaded rats. Free-water reabsorption was converted to free-water clearance. Natriuretic doses of both peptides had no significant effect on glomerular filtration rate. Higher doses of [2,4-diisoleucine]-oxytocin produced a small increase in the blood pressure. [4-Leucine]-oxytocin, on the other hand, produced a transient decrease in the blood pressure. However, it had no inhibitory activity on the vasopressor response to vasopressin. These findings suggest that the antidiuretic, the natriuretic and the vasopressor activities of vasopressin and oxytocin involve three distinct receptor mechanisms, each having a certain degree of structural specificity.

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