title: Effects of a specific inhibitor of the vascular action of vasopressin in humans.
abstract: Experimental evidence indicates that arginine vasopressin (AVP) may contribute to the rise of blood pressure (BP) in hypertension induced by renal failure and sodium overload. We studied the AVP inhibitor [1-(B-mercapto-B,B-cyclopentamethylenepropionic acid)-2-(O-methyl)tyrosine] AVP in 12 normal and seven hypertensive subjects with end-stage renal disease. To test the agent's capacity to block the pressor action of exogenous AVP In humans, we constructed a dose-response curve with AVP doses of 1 to 20 mU/kg, raising BP by up to 30 mm Hg. Subsequently, five volunteers receive intravenous (i.v.) doses of 0.1 mg, and five volunteers received 0.5 mg of the inhibitor. The dose-response curve was then repeated with AVP doses up to 200 mU/kg. Both doses of the inhibitor shifted the curve to the right and downward, with the BP response to 20 mU/kg AVP being inhibited by 23% and 80% respectively. The duration of action of the compound was tested in two additional subjects, and was found to be over 3 hours. We then tested the compound in seven hypertensive patients with end-stage renal failure. Two days before dialysis, patients received a 150 mEq/day Na diet. After an additional Na load of 180 mEq via i.v. saline over 3 hours under constant BP and ECG monitoring, they received an i.v. bolus of 0.5 mg AVP inhibitor. A moderate BP fall occurred in five patients; it was maximal at 45 to 60 minutes and returned to baseline by 70 to 90 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D008297:Male; D012016:Reference Values; D012965:Sodium Chloride; D013997:Time Factors
chemical_list: D001127:Arginine Vasopressin; D012965:Sodium Chloride; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-