DDAVP (1-desamino-8-D-arginine vasopressin): an antagonist of the pressor action of endogenous vasopressin?
The pressor effect of arginine vasopressin (AVP) is thought to be mediated by a calcium-dependent mechanism (V1-receptor) whereas its antidiuretic effect depends on c-AMP (V2-receptor). 1-Desamino-8-D-arginine-vasopressin (DDAVP) is possibly an antagonist on the V1-receptor and may therefore be used for assessing the role of endogenous AVP in blood pressure regulation. This possibility was tested using the following models: aggregation of human platelets, renin secretion by rabbit kidney slices, and blood pressure and renin responses in normal human subjects (n = 11) and patients with autonomic insufficiency (n = 4). AVP 10(-10)-10(-7) mol/l caused dose-dependent platelet aggregation and inhibition of renin secretion. These effects were absent in a calcium free medium or in the presence of the calcium antagonist verapamil 5 X 10(-5) mol/l. DDAVP up to 10(-5) mol/l had no effect but shifted the dose-response curves of AVP to the right. AVP infusion into normal subjects is known to lower heart rate and plasma renin with little change in blood pressure. DDAVP 400 ng/kg in 10 min caused no change in systolic pressure but diastolic pressure was lowered by 14 +/- 2 mmHg (mean +/- s.e.m.). Heart rate rose by 24 +/- 2 beats/min and renin rose from 21 +/- 4 to 57 +/- 9 muu/ml (P less than 0.01). In the patients with autonomic insufficiency both systolic and diastolic pressures fell by 20-50 mmHg after DDAVP 200 ng/kg without any change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D012016:Reference Values; D012083:Renin / Q000378:metabolism; D014667:Vasopressins / Q000502:physiology*
D014667:Vasopressins; D001127:Arginine Vasopressin; D012083:Renin; D003894:Deamino Arginine Vasopressin; D009638:Norepinephrine