Involvement of presynaptic dopamine receptors in the antihypertensive response to 2-NN-dimethylamino-5,6-dihydroxy-1,2,3,4,-tetrahydronaphthalene (M-7).
M-7, 1 and 3 mg kg-1 s.c., elicits an antihypertensive response and bradycardia in conscious spontaneously hypertensive rats (SHR) and causes inhibition of stimulation-evoked pressor response and tachycardia in pithed SHR. Metoclopramide (30 mg kg-1 i.p.), but not piperoxan (5 mg kg-1 i.p.), abolished the antihypertensive effect and inhibition of stimulation-evoked pressor responses produced by M-7 (1 mg kg-1 s.c.) in SHR. Conversely, piperoxan, but not metoclopramide, reduces the bradycardia and inhibition of stimulation-evoked tachycardia produced by M-7. Metoclopramide (30 mg kg-1 i.p.) did not affect the cardiovascular responses elicited by intracerebroventricular administration of either clonidine (1 microgram) of M-7 (3 micrograms). These results suggest that the antihypertensive effect of M-7 may be mediated by stimulation of presynaptic dopamine receptors on sympathetic nervous to the vasculature and is independent of the bradycardia, which is probably due to stimulation of presynaptic alpha 2-adrenoceptors on cardiac sympathetic nerve endings.
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009284:Naphthols / Q000494:pharmacology*; D010883:Piperoxan / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects
D000959:Antihypertensive Agents; D009284:Naphthols; D011954:Receptors, Dopamine; C009957:5,6-dihydroxy-2-dimethylaminotetralin; D010883:Piperoxan; D003000:Clonidine