Hemodynamic Effects of Antagonists of the Vasoconstrictor Action of Vasopressin in Conscious Dogs

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Abstract
Two antagonists of the pressor action of arginine-vasopressin (AVP) were studied in conscious, normally hydrated dogs, i.e., 1-deaminopenicillamine-4-valine-8-D-arginine-vasopressin, or dPVDAVP, and 1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylene propionic acid)2-(O-methyl)tyrosine arginine-vasopressin, or d(CH2)5Tyr(Me)AVP. The hemodynamic effects of these antagonists when given alone were examined. The infusion of dPVDAVP, 200 ng/kg per min, increased cardiac output (measured with an aortic electromagnetic flowmeter) by 23% and heart rate by 27%, leaving arterial pressure unchanged. Most of the change in cardiac output reflected a large increase in skeletal muscle blood flow, as determined by radioactive microspheres. The injection of d(CH2)5Tyr(Me)AVP, 10 .mu.g/kg, had little effect on cardiac output, arterial pressure and heart rate. The ability of the 2 antagonists to block the hemodynamic responses to injections of AVP was then examined. In the absence of the antagonists, AVP induced dose-related increases in mean arterial pressure and total peripheral resistance, as well as decreases in heart rate and cardiac output. The antagonist dPVDAVP shifted the dose-response curves to the right without changing their slope. The hemodynamic response to AVP was strikingly modified following blockade with d(CH2)5Tyr(Me)AVP. Cardiac output and heart rate increased, whereas total peripheral resistance decreased, for doses of AVP between 25 and 400 ng/kg. Some antagonists of the pressor action of vasopressin may influence hemodynamics of conscious dogs by effects other than competitive antagonism at the level of vascular receptors.