Metoclopramide and domperidone block the antihypertensive effect of bromocriptine in hypertensive patients.
This study was conducted in normotensive and hypertensive subjects at the Vargas Hospital of Caracas. Normotensive subjects received, in a cross-over fashion, placebo, metoclopramide (MTC), or domperidone (DOMP), 40 mg of each drug, daily for 1 week. The first group of patients under placebo for 1 week received a single 2.5-mg oral dose of bromocriptine (Br). The second group of patients received 30 mg MTC daily (divided into three doses) for 1 week. At the end of the period a single dose of 2.5 mg Br was administered to each patient. The third group of eight hypertensive patients received DOMP for 1 week at 30 mg/d and then a single 2.5-mg Br dose. Cardiovascular and biochemical parameters including arterial pressure, heart rate, plasma renin activity, and plasma aldosterone were evaluated during the 6-hour period before and after the administration of Br. Neither DOMP nor MTC significantly modified blood pressure and heart rate in normotensive patients. Br reduced both systolic and diastolic arterial pressure in hypertensive subjects. The peak of the antihypertensive effect appeared 3 hours after drug administration, but reduction of arterial pressure lasted approximately 6 hours. At the same time, Br reduced plasma aldosterone levels and plasma renin activity. MTC and DOMP reversed the antihypertensive effect of Br and its effect on aldosterone levels and plasma renin activity. We conclude from these findings that Br acts as an antihypertensive agent at peripheral and central levels by stimulating dopamine-2 receptors, which are involved in the aldosterone and renin secretion.
Luchsinger
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Address for correspondence: Apartado Postal 76333, El Marqués, Caracas 1070A, Caracas, Venezuela.
Grilli
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Velasco
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D000328:Adult; D000450:Aldosterone / Q000097:blood; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004294:Domperidone / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012083:Renin / Q000097:blood / Q000187:drug effects
D000959:Antihypertensive Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D000450:Aldosterone; D004294:Domperidone; D012083:Renin; D008787:Metoclopramide