Dopaminergic control of angiotensin II-induced vasopressin secretion in vitro

Abstract

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 μM dopamine, 307 ± 66% ⋅ explant−1 ⋅ h−1, 1 μM SKF-38393, 369 ± 41% ⋅ explant−1 ⋅ h−1, and 0.1 μM apomorphine, 374 ± 67% ⋅ explant−1 ⋅ h−1. Selective D1 antagonism with 1 μM SCH-23390 blocked AVP secretion to values no different from basal. Domperidone (D2 antagonist), phenoxybenzamine (nonselective adrenergic antagonist), and prazosin (α1-antagonist) failed to prevent release. D1 antagonism also prevented AVP secretion to 1 μM angiotensin II [angiotensin II, 422 ± 87% ⋅ explant−1 ⋅ h−1vs. angiotensin II plus SCH-23390, 169 ± 28% ⋅ explant−1 ⋅ h−1( P < 0.05)], but D2 and α1-adrenergic blockade did not. In contrast, AT1 receptor inhibition with 0.5 μM losartan blocked angiotensin II- but not dopamine-induced AVP release. AT2antagonism had no effect. Although subthreshold doses of the agonists did not increase AVP secretion (0.05 μM dopamine, 133 ± 44% ⋅ explant−1 ⋅ h−1; 0.01 μM SKF-38393, 116 ± 26% ⋅ explant−1 ⋅ h−1;and 0.001 μM 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.