Humoral effects of metoclopramide and domperidone in normal subjects and in hypertensive patients.
To evaluate whether, in humans, metoclopramide (MCP), a DA2 antagonist which readily crosses the brain-blood barrier, can stimulate plasma aldosterone (ALD) through hypophyseal-adrenal axis activation in addition to its direct adrenal antidopaminergic activity, we have investigated the effects of MCP and domperidone (DMP), a specific antagonist of peripheral DA2 receptors, on plasma ALD, adrenocorticotropin (ACTH), cortisol and prolactin (PRL) in 15 subjects. Ten controls and 5 uncomplicated essential hypertensive patients, in whom the dopaminergic tone is hypothesized to be reduced, received, according to a single-blind randomized procedure, MCP (10 mg iv) or DMP (10 mg iv) and, after an interval of at least 1 week, the reverse treatment. MCP and DMP similarly increased PRL (p less than 0.001), while only MCP significantly increased plasma ALD (p less than 0.01), ACTH (p less than 0.02) and cortisol (p less than 0.02) both in normotensives and in hypertensives, without any difference between them. These data confirm that, in spite of similar DA2 antagonistic potency of the two drugs, only MCP is able to increase plasma ALD. Since MCP significantly increased also ACTH levels we cannot exclude an involvement of this hormone on MCP-induced ALD release. Finally, the similar PRL and ALD response in normotensives and hypertensives does not support the hypothesis of a reduced dopaminergic system activity in essential hypertensives.
Bernini
G P
GP
Clinica Medica I, Università di Pisa, Italy.
Lucarini
A R
AR
Franchi
F
F
Salvetti
A
A
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000450:Aldosterone / Q000097:blood; D004294:Domperidone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D008875:Middle Aged; D011388:Prolactin / Q000097:blood; D012016:Reference Values
D000450:Aldosterone; D004294:Domperidone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D008787:Metoclopramide; D006854:Hydrocortisone