Dopaminergic control of angiotensin II-induced vasopressin secretion in vitro.

Because dopamine influences arginine vasopressin (AVP) release, the present studies were designed to ascertain the dopamine receptor subtype that potentiates angiotensin II-induced AVP secretion in cultured hypothalamo-neurohypophysial explants. Dopamine (a nonselective D1/D2 agonist), apomorphine (a D2 >> D1 agonist), and SKF-38393 (a selective D1 agonist) dose dependently increased AVP secretion. Maximal AVP release was observed with 5 microM dopamine, 307 +/- 66% . explant-1 . h-1, 1 microM SKF-38393, 369 +/- 41% . explant-1 . h-1, and 0.1 microM apomorphine, 374 +/- 67% . explant-1 . h-1. Selective D1 antagonism with 1 microM SCH-23390 blocked AVP secretion to values no different from basal. Domperidone (D2 antagonist), phenoxybenzamine (nonselective adrenergic antagonist), and prazosin (alpha1-antagonist) failed to prevent release. D1 antagonism also prevented AVP secretion to 1 microM angiotensin II [angiotensin II, 422 +/- 87% . explant-1 . h-1 vs. angiotensin II plus SCH-23390, 169 +/- 28% . explant-1 . h-1 (P < 0.05)], but D2 and alpha1-adrenergic blockade did not. In contrast, AT1 receptor inhibition with 0.5 microM losartan blocked angiotensin II- but not dopamine-induced AVP release. AT2 antagonism had no effect. Although subthreshold doses of the agonists did not increase AVP secretion (0. 05 microM dopamine, 133 +/- 44% . explant-1 . h-1; 0.01 microM SKF-38393, 116 +/- 26% . explant-1 . h-1;and 0.001 microM angiotensin II, 104 +/- 29% . explant-1 . h-1 ), the combination of dopamine and angiotensin II provoked a significant rise in AVP [420 +/- 83% . explant-1 . h-1 (P < 0.01)]. Similar results were observed with SKF-38393 and angiotensin II, and the AVP response was blocked to basal levels by either D1 or AT1 antagonism. These findings support a role for D1 receptor activation to increase AVP release and mediate angiotensin II-induced AVP release within the hypothalamo-neurohypophysial system. The data also suggest that the combined subthreshold stimulation of receptors that use distinct intracellular pathways can prompt substantial AVP release.