Prevention of alpha-adrenergic coronary constriction by calcium-antagonists.
This manuscript reviews the experimental evidence for a functional antagonism of Ca-antagonists against alpha-adrenoceptor-mediated increases in coronary vasomotor tone. In studies on anesthetized dogs, intravenous nifedipine effectively prevented the alpha 1-adrenoceptor-mediated increase in epicardial coronary resistance, as well as the increase in end-diastolic resistance mediated by both alpha 1- and alpha 2-adrenoceptors during cardiac sympathetic nerve stimulation. Both intracoronary and intravenous administration of nifedipine also prevented the alpha 2-adrenoceptor-mediated increase in coronary resistance distal to severe stenoses, as well as the resulting ischemic dysfunction and net lactate production during cardiac sympathetic nerve stimulation. Felodipine was equally effective as nifedipine in preventing an alpha 2-adrenoceptor-mediated increase in coronary resistance and the resulting contractile dysfunction distal to severe coronary stenoses. alpha 1- and alpha 2-Adrenergic coronary constriction also contribute to the severity of myocardial ischemia in conscious dogs during treadmill exercise. Again, nifedipine improved regional myocardial blood flow and attenuated regional contractile dysfunction during exercise-induced ischemia in conscious dogs with a chronic coronary stenosis. This beneficial effect of nifedipine was attributed to a recruitment of coronary dilator reserve and not to a reduction in heart rate or afterload. In conclusion, there is solid experimental evidence for a functional antagonism of Ca-antagonists against alpha-adrenergic coronary constriction and its contribution to myocardial ischemia.
Heusch
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G
Abteilung Pathophysiologie, Universitätsklinikum Essen, FRG.
Deussen
A
A
Guth
B D
BD
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003251:Constriction, Pathologic; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology; D004285:Dogs; D015736:Felodipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D009543:Nifedipine; D015736:Felodipine