Dopamine-induced coronary effects in the dog heart attributed to beta- and alpha-adrenergic mechanisms.
Open chest anesthetized dogs were given dopamine (DA) in intravenous (i.v., 2-16 micrograms.kg-1.min-1) and intracoronary (i.c., 10-40 micrograms.min-1) infusions. The drug effect was analyzed using the nonselective beta-adrenoceptor antagonist oxprenolol (0.5 mg.kg, i.v.) and the nonselective alpha-adrenoceptor antagonist phentolamine (1.0 mg.kg-1, i.v.). Coronary blood flow (CBF, electromagnetic flowmeter), arterial pressure and left ventricular contractile force (strain gauge) were measured. Coronary vascular responses were characterized by changes of CBF and calculated coronary vascular resistance (CVR). In the control state, DA-induced arterial hypertension (i.v. administration) and augmented inotropism (i.v. and i.c. administration) were accompanied by a dose-dependent coronary vasodilatation (increase of CBF and decrease of CVR). Oxprenolol converted coronary vasodilatation to vasoconstriction during DA infusions and blocked the inotropic action; the hypertensive DA effect remained unaffected. Similar alterations were observed after a transitory (45 min) regional myocardial ischemia, elicited by coronary occlusion. On the other hand, phentolamine-pretreatment potentiated the DA-induced coronary vasodilatation and converted hypertension to hypotension; the inotropic component of the DA action was not affected. After combined beta- and alpha-blockade, DA failed to increase CBF and decrease CVR during the infusion periods. Instead, the drug elicited a very slight coronary vasoconstriction. I.c. (but not i.v.) infusions of DA were regularly followed by a rebound-like, transient CBF increase, even after combined beta- and alpha-blockade. These results show that all of the multifactorial determinants of the direct, steady state coronary effects of DA can be ascribed to alpha- and beta-adrenoceptor stimulation, whereas the hypothetical dopaminergic coronary vascular receptors do not seem to play a decisive role in these responses. However, undefined after-effects provoked by i.c. DA, may be connected with specific dopaminergic effects.
Rabloczky
G
G
Institute of Drug Research, Budapest, Hungary.
Kékesi
V
V
Mader
M R
MR
Juhász-Nagy
A
A
D000818:Animals; D001337:Autonomic Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D010096:Oxprenolol / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D001337:Autonomic Agents; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010096:Oxprenolol; D004298:Dopamine; D010646:Phentolamine