Effect of nonpeptide angiotensin AT-1 and AT-2 antagonists on isoproterenol-induced renin release.

The AT-1 receptor antagonist, losartan potassium, produced a large rise in plasma renin activity (PRA) after peripheral, but not intracerebroventricular (ICV), administration. Peripheral, but not ICV administration of losartan also augmented the release of renin induced by peripheral administration of the beta-adrenergic agonist, isoproterenol. The increase in PRA induced by losartan plus isoproterenol was greater than the sum of the increases in PRA induced by the individual treatments. There was, however, no significant enhancement of the hypotensive action of isoproterenol by peripherally administered losartan. The AT-2 receptor antagonist, PD 123319, produced no increase in PRA after either peripheral or ICV injection. However, peripheral injection of PD 123319 slightly increased PRA after peripheral administration of isoproterenol. The data are discussed in terms of the relationship between renin-angiotensin systems and fluid intake, with special reference to the failure of peripherally administered losartan to block isoproterenol-induced water intake.