Effects of different dopaminergic antagonists on bromocriptine-induced inhibition of norepinephrine release

In this study we evaluated the effects of placebo or acute bromocriptine (BC) administration (2.5 mg orally) on plasma catecholamines, systolic and diastolic blood pressure (BP), heart rate, and plasma PRL in six normal subjects [group I, mean age 33.2 +/- 5.4 (SD) yr] in the supine as well as upright position. BC induced a significant decrease in plasma norepinephrine in the supine [167.7 +/- 16.8 (SEM) vs. 101.9 +/- 33.7 pg/ml, P less than 0.005] and upright positions [397.3 +/- 27.7 vs. 211.3 +/- 26.7 pg/ml, P less than 0.005], a decrease in systolic and diastolic BP and a decrease in plasma PRL (P less than 0.01). After standing, epinephrine levels increased significantly (53.6 +/- 11.8 vs. 226.4 +/- 71.0 pg/ml, P less than 0.05). The study was repeated in a second group of seven normal subjects (mean age, 32.3 +/- 12.9 yr) after placebo or metoclopramide (20 mg orally) plus BC. In this group metoclopramide, a central and peripheral antidopaminergic agent, counteracted the BC-induced effects found in group I, both in the basal and stimulated conditions. Plasma PRL increased significantly (P less than 0.025). Finally, to assess the effect of peripheral dopaminergic blockade on BC-induced changes in sympathetic outflow, we repeated the study in seven normal subjects (group III, mean age, 30.1 +/- 5.0 yr) after placebo or domperidone (20 mg orally) plus BC. Domperidone blocked the effects of BC on norepinephrine and BP in the supine position. On standing there was a significant decrease in systolic (P less than 0.05) and diastolic (P less than 0.05) BP and an increase in epinephrine levels (58.9 +/- 12.2 vs. 109.8 +/- 24.6 pg/ml, P less than 0.05) was still observed. Plasma PRL increased significantly (P less than 0.025). The results of this study suggest that the inhibition of sympathetic outflow induced by BC is peripherally mediated. As peripheral dopamine receptor blockade did not counteract all the effects after BC during standing, dopaminergic modulation of central reflex sympathetic activation is suggested.