Plasma Half-Lives of Vasopressin and Oxytocin Analogs After iv Injection in Rats

Abstract

Although many workers have measured the plasma half-lives of oxytocin and vasopressin in rats (l), there have been few studies on the half-lives of structural analogs of vasopressin and oxytocin. This is largely due to the lack of suitable radioimmunoassay methods and the difficulties inherent in measuring peptides in plasma by bioassays. Studies on the rates of elimination from plasma of analogs of the neurohypophysial hormones could provide information on the manner in which the endogenous hormones are metabolized. I have, therefore, applied a new method for estimating plasma half-lives from vasopressor responses (2) to a series of analogs of vasopressin and oxytocin in an effort to determine which structural changes can delay elimination from the plasma. From such information one may speculate on the types of enzymatic inactivation that are important for the elimination of arginine-vasopressin and oxytocin and whether these are different for these two hormones. Materials and methods.To screen for possible long-acting analogs, I first looked through several years' records of vasopressor assays done on vasopressin and oxytocin analogs in Dr. W. H. Sawyer's laboratory. If I could mask identification of the injections and consistently distinguish the responses to the test analog as longer than the responses to the standard, I considered the analog as a candidate for half-life studies. The analogs which could be so distinguished were [8-ornithinel-oxytocin, [8-arginine]-vasotocin, and deaminated analogs of vasopressin. Guided largely by this survey, I decided to concentrate on measuring the half-lives of analogs modified in the one position, the eight position, and the one and six positions.Female Sherman rats (from Camm Research) were used throughout. They were prepared as for vasopressor assay, and the pressor responses to a series of intravenous injections of each analog were analyzed to obtain a plasma half-life by the curve-fit method, as previously described (2). The series of injections was 1, 2,4, 8, and 32 pressor mU of peptide, given in ascending order of dose, in all instances. A new injection was given only after blood pressure had returned to normal for 10-15 min. Each rat was used to study two peptides. In the instances in which two peptides were found to have significantly different mean half-lives as determined from separate groups of rats, the longer-acting peptide was also longer-acting when the two peptides were compared in an individual rat.Peptides used for half-life determinations were arginine-vasopressin, lysine-vasopressin, arginine-vasotocin, oxytocin, " 1 -hydroxy-arginine-vasopressin"([ 1 -~-2 -h ydroxy-3-mercaptopropionic acidl-argininevasopressin), " 1 -hydroxy-oxytocin", [ 8-ornithinel-oxytocin, [8-glutamine]-oxytocin, [ 8proline] -oxytocin, "deamino -dicarba-arginine-vasopressin" ([ 1,6-aminosuberic acid]arginine-vasopressin), and deamino-dicarbaarginine-vasotocin. Some of the data on halflives of arginine-vasopressin, arginine-vasotocin, and deamino-arginine-vasopressin have been re...

Central Action of Increased Osmolality to Support Blood Pressure in Deoxycorticosterone Acetate–Salt Rats

“…This time course is consistent with the half-life of vasopressin of a few minutes. [41][42][43] On the other hand, based on the rapid time course, the initial immediate fall is likely because of sympathetic withdrawal. This conclusion is supported by the studies in animals in which both the vasopressin and sympathetic inputs were blocked, because decreasing forebrain OSM had no further effect on BP.…”

Release of oxytocin induced by salt loading and its influence on renal excretion in the male rat.

“…As a large fall in arterial blood pressure can cause the release of neurohypophysial hormone (Poulain, Wakerley & Dyball, 1977) it was important to minimize the fall. In view of the short biological half-life (approximately 2-3 min) of oxytocin (Fabian et al 1969;Gazis, 1978), only samples obtained within 45 sec of stopping oxytocin infusion were assayed.…”

The Design of Effectivein VivoAntagonists of Rat Uterus and Milk Ejection Responses to Oxytocin*

“…This may relate to the observation that [8-ornithine]oxytocin has an apparently longer plasma half-life in rats than does oxytocin (30). Competitive antagonists of oxytocin would be most useful experimentally if they were highly specific and essentially devoid of agonistic activities characteristic of neurohypophysial peptides.…”