vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Dehydration

Despite the known potent vasoconstrictor effects of vasopressin, the role of this hormone in the maintenance of blood pressure is incompletely understood. In studies performed in animals with increased plasma vasopressin concentrations, several complex cardiovascular effects have been noted, including decreases in heart rate and cardiac output, which may account for a lack of effect on arterial pressure despite the vasopressin-induced increase in total peripheral resistance. Only a few studies have been done to assess the cardiovascular effects of vasopressin in human subjects, and most of these have been limited to measurement of heart rate and arterial pressure only. The present study was designed to identify more fully the cardiovascular effects of vasopressin when plasma vasopressin concentrations are increased by osmotic stimulation without the superimposition of major nonosmotic stimuli associated with severe volume depletion.. Studies were performed on 11 normal human subjects in supine and erect posture before and after 24 hours of fluid deprivation, and following administration of a selective V1 receptor antagonist, [d(CH2)5Tyr(ME)]AVP, after dehydration. Cardiovascular parameters were measured noninvasively by thoracic electrical bioimpedance cardiography and blood samples for measurements of plasma concentrations of vasopressin and other hormones affected by dehydration and differences in posture were collected for subsequent analysis.. After 24 hours of fluid restriction, plasma osmolality was increased from 287 +/- 0.9 to 294 +/- 0.7 mosm/kg H20 and plasma vasopressin concentrations (Pavp) were increased in both supine and erect posture. Mean arterial (MAP) and systolic blood pressure (SBP) were reduced by fluid restriction but were higher in erect than in supine posture both before and after fluid restriction. Heart rate (HR), diastolic blood pressure (DBP), and systemic vascular resistance (SVRI) were also higher in erect than in supine posture, while cardiac index (CI), stroke index (SI), end-diastolic index (EDI), and an index of total thoracic fluid content (TFC) were all reduced in erect posture, both before and after dehydration. Plasma renin activity (PRA) and plasma norepinephrine concentrations (Pne) were increased in erect posture, both before and after dehydration, but there was no effect of erect posture on plasma vasopressin concentrations (Pavp), either before or after dehydration. Administration of the V1 receptor antagonist after dehydration had no effect on hemodynamic parameters other than small reductions in DBP and cardiac preload.. It is concluded from these studies that small increases in Pavp associated with moderate dehydration do not play a role in the maintenance of arterial pressure in normal human subjects in either supine or erect posture.

Topics: Adult; Aged; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Dehydration; Female; Hemodynamics; Hormone Antagonists; Humans; Male; Middle Aged; Posture; Vasoconstrictor Agents; Vasopressins

In view of our previous findings that a specific antidiuretic (V2) agonist, 4-valine-8-D-arginine vasopressin, acutely increased cardiac output and heart rate in dogs, we examined the hypothesis that interaction with V2-like receptors might contribute to the hemodynamic response seen after blockade of the vasoconstrictor (V1) effect of arginine-vasopressin in dehydrated dogs. After 48 hours of water restriction which increased plasma vasopressin to 10.6 +/- 2.0 pg/ml, the V1 antagonist 1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 2-(O-methyl)tyrosine arginine-vasopressin, 10 micrograms/kg, was injected intravenously into six conscious dogs, and the combined V1 + V2 antagonist 1-(beta-mercapto-beta,beta,cyclopentamethylene propionic acid) 2-(O-ethyl)-D-tyrosine, 4-valine arginine-vasopressin, 10 micrograms/kg, was administered to another six dogs. Mean arterial pressure, cardiac output (electromagnetic flowmeter), and regional blood flows (radioactive microspheres) were measured before and 20-30 minutes after antagonist administration. Mean arterial pressure did not change significantly in either instance. Cardiac output increased by 31.0 +/- 7.1% after V1 blockade, but by only 10.8 +/- 2.1% following V1 + V2 blockade. Blood flow increased significantly and to a similar extent in the skin, the skeletal muscles, and the fat following both antagonists. Conversely, kidney, arterial liver, and bone blood flow increased only after V1 blockade. In six additional, normally hydrated conscious dogs, it was shown that the V1 + V2 antagonist had no significant hemodynamic effects, a finding previously established for the V1 antagonist. The V1 + V2 antagonist completely prevented the hemodynamic effects associated with administration of the V2 agonist 4-valine-8-D-arginine vasopressin, 200 ng/kg, whereas the V1 antagonist did not. Both antagonists had similar effects on the hemodynamic changes induced by nitroprusside infusion, namely a potentiation of the blood pressure lowering action. These results suggest that part of the hemodynamic response to blockade of the vasoconstrictor action of vasopressin in dehydration is caused by unmasking cardiovascular effects linked to the antidiuretic activity of the arginine-vasopressin molecule.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Bone and Bones; Cardiac Output; Cardiovascular Physiological Phenomena; Cardiovascular System; Dehydration; Dogs; Hemodynamics; Kidney; Liver; Male; Vascular Resistance; Vasoconstriction