DOPAMINERGIC CONTROL OF ANGIOTENSIN-II-INDUCED VASOPRESSIN SECRETION IN-VITRO

Because dopamine influences arginine vasopressin (AVP) release, the pr esent studies were designed to ascertain the dopamine receptor subtype that potentiates angiotensin II-induced AVP secretion in cultured hyp othalamo-neurohypophysial explants. Dopamine (a nonselective D-1/D-2 a gonist), apomorphine (a D-2 much greater than D-1 agonist), and SKF-38 393 (a selective D-1 agonist) dose dependently increased AVP secretion . Maximal AVP release was observed with 5 mu M dopamine, 307 +/- 66%.e xplant(-1).h(-1), 1 mu M SKF-38393, 369 +/- 41%.explant(-1).h(-1), and 0.1 mu M apomorphine, 374 +/- 67%.explant(-1).h(-1). Selective D-1 an tagonism with 1 mu M SCH-23390 blocked AVP secretion to values no diff erent from basal. Domperidone (D-2 antagonist), phenoxybenzamine (nons elective adrenergic antagonist), and prazosin (alpha 1-antagonist) fai led to prevent release. D-1 antagonism also prevented AVP secretion to 1 mu M 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 D-2 and alpha(1)-adrenergic blockade did not. In contrast, AT(1) receptor inhibition with 0.5 mu M losartan blocked angiotensin II- but not dopamine-induced AVP release. AT(2) antagonism had no effe ct. Although subthreshold doses of the agonists did not increase AVP s ecretion (0.05 mu M dopamine, 133 +/- 44%.explant(-1).h(-1); 0.01 mu M SKF-38393, 116 +/- 26%.explant(-1).h(-1); and 0.001 mu M angiotensin II, 104 +/- 29%.explant(-1).h(-1)), the combination of dopamine and an giotensin 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 e ither D-1 or AT(1) antagonism. These findings support a role for D-1 r eceptor activation to increase AVP release and mediate angiotensin II- induced AVP release within the hypothalamo-neurohypophysial system. Th e data also suggest that the combined subthreshold stimulation of rece ptors that use distinct intracellular pathways can prompt substantial AVP release.