Desamino-8 d-arginine vasopressin treatment of Brattleboro rats: Effect on sensitivity to pressor hormones

Abstract

The cardiovascular effects of intravenous injections of vasopressin, angiotensin II and noradrenaline were studied in anaesthetized adult male Brattleboro rats with hereditary diabetes insipidus on lifelong treatment with the vasopressin V 2 receptor agonist desamino-8 d-arginine vasopressin in the drinking fluid, which restored fluid input and output to normal rat values. The pressor response to 20 ng·kg −1 vasopressin was significantly greater ( P < 0.005) in the vasopressin V 2 receptor agonist-treated rats than in the control animals, but the responses to all higher doses of the peptide were comparable. Doses of noradrenaline from 40 to 160 ng·kg −1 had similar pressor effects in the treated and control rats, while the pressor response to the highest dose of noradrenaline (320 ng·kg −1) was significantly lower ( P < 0.01) in the vasopressin V 2 receptor agonist-treated rats. Furthermore the pressor response to all three doses of angiotensin II (40, 80 and 160 ng·kg −1) were significantly attenuated in the treated rats compared to the control group ( P < 0.001, P < 0.05 and P < 0.0005 respectively), as were the decreases in heart rate ( P < 0.005 at 40 ng·kg −1, P < 0.01 at 80 ng·kg −1). The hypovolaemic stimulus induced by a blood loss of 20 ml·kg −1 resulted in a lower mean arterial blood pressure initially in the treated Brattleboro rats, but subsequent recovery was similar in both treated and control groups. In contrast, no significant differences in responsiveness to the three pressor hormones or in blood pressure recovery following haemorrhage were found between anaesthetized Brattleboro rats infused with desamino-8 d-arginine vasopressin on the day of study only, and control animals. These results suggest that long-term treatment of Brattleboro rats with diabetes insipidus with the vasopressin V 2 receptor agonist, which corrects the urinary concentrating defect, has subtle cardiovascular effects associated with interactions with pressor hormones, particularly angiotensin II.