Rabloczky G, Kékesi V, Mader M R, Juhász-Nagy A
Institute of Drug Research, Budapest, Hungary.
Arch Int Pharmacodyn Ther. 1988 May-Jun;293:109-26.
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.
对开胸麻醉犬静脉输注多巴胺（DA，2 - 16微克·千克⁻¹·分钟⁻¹）和冠状动脉内输注多巴胺（10 - 40微克·分钟⁻¹）。使用非选择性β - 肾上腺素能受体拮抗剂氧烯洛尔（0.5毫克·千克，静脉注射）和非选择性α - 肾上腺素能受体拮抗剂酚妥拉明（1.0毫克·千克⁻¹，静脉注射）分析药物作用。测量冠状动脉血流量（CBF，电磁流量计）、动脉压和左心室收缩力（应变片）。冠状动脉血管反应以CBF变化和计算的冠状动脉血管阻力（CVR）来表征。在对照状态下，DA诱导的动脉高血压（静脉给药）和正性肌力作用增强（静脉和冠状动脉内给药）伴随着剂量依赖性的冠状动脉血管舒张（CBF增加和CVR降低）。在输注DA期间，氧烯洛尔使冠状动脉血管舒张转变为血管收缩，并阻断正性肌力作用；DA的高血压作用不受影响。在冠状动脉闭塞引起短暂性（45分钟）局部心肌缺血后，观察到类似的改变。另一方面，酚妥拉明预处理增强了DA诱导的冠状动脉血管舒张，并使高血压转变为低血压；DA作用的正性肌力成分不受影响。在联合β和α受体阻断后，在输注期间DA未能增加CBF和降低CVR。相反，该药物引起非常轻微的冠状动脉血管收缩。即使在联合β和α受体阻断后，冠状动脉内（而非静脉内）输注DA后通常会出现类似反弹的短暂CBF增加。这些结果表明，DA直接、稳态冠状动脉效应的所有多因素决定因素都可归因于α和β肾上腺素能受体刺激，而假设的多巴胺能冠状动脉血管受体在这些反应中似乎不起决定性作用。然而，冠状动脉内DA引发的未明确的后效应可能与特定的多巴胺能效应有关。
