Abstract

The vascular effects of arginine vasopressin (AVP) were examined in conscious Sprague-Dawley rats. In six control rats, synthetic AVP at a dose of 40 ng/kg, injected as an intravenous bolus, resulted in a rise in mean arterial blood pressure (BP) from 127 to 149 mm Hg (P < 0.005). No tachyphylaxis was observed after a second AVP bolus administered 30 min later, as BP increased from 125 to 150 mm Hg, P < 0.005. In a second group of six rats, 1-deamino penicillamine, 2-(O-methyl) tyrosine AVP ([dPTyr (Me)]AVP), was administered intravenously at a dose of 10 μg/kg, just before the second AVP bolus. In this group of studies BP rose from 124 to 150 mm Hg (P < 0.01) after the first AVP bolus, but not after the second AVP bolus, which was administered after [dPTyr (Me)]AVP (129 vs. 129 mm Hg, NS). To assess the effect of this AVP pressor antagonist on BP in rats with suppressed endogenous vasopressin, six water-diuresing rats (mean urinary osmolality, 99 mosmol/kg H2O) were administered the analogue at the same dose as the first group of rats. The analogue exerted no demonstrable effect on mean BP (128 before vs. 129 mm Hg after [dPTyr (Me)]AVP, NS). In these rats, mean radioimmunoassayable levels of AVP were at or below the detectable limits of our assay (0.5 pg/ml). In contrast, six rats in which endogenous AVP was stimulated by fluid deprivation for 24 h (mean urinary osmolality, 2,489 mosmol/kg H2O and mean AVP level of 21.6 pg/ml) had a marked fall in BP when administered the AVP analogue. In these animals [dPTyr (Me)]AVP caused a fall in BP from 124 to 110 mm Hg (P < 0.005). This fall in blood pressure was due to a fall in peripheral vascular resistance (0.35 vs. 0.30 mm Hg/ml per min per kg, P < 0.02) after [dPTyr (Me)]AVP, as cardiac index remained unchanged.

Authors

Gary A. Aisenbrey, William A. Handelman, Patricia Arnold, Maurice Manning, Robert W. Schrier

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