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Prevention of alpha-adrenergic coronary constriction by calcium-antagonists
Abstract:
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.
Insights
Calcium (Ca) antagonists, like nifedipine and felodipine, effectively counteract alpha-adrenoceptor-mediated coronary constriction. This action helps prevent myocardial ischemia and improves blood flow during stress, highlighting their therapeutic potential.
Area of Science:
- Cardiovascular Pharmacology
- Myocardial Ischemia Research
Background:
- Alpha-adrenoceptors play a role in regulating coronary vasomotor tone.
- Alpha-adrenergic coronary constriction can exacerbate myocardial ischemia.
Purpose of the Study:
- To review experimental evidence on the functional antagonism of calcium (Ca) antagonists against alpha-adrenoceptor-mediated coronary vasoconstriction.
- To assess the impact of Ca antagonists on myocardial ischemia induced by alpha-adrenergic stimulation.
Main Methods:
- Studies involved anesthetized and conscious dogs.
- Administration of Ca antagonists (nifedipine, felodipine) via intravenous and intracoronary routes.
- Assessment of coronary resistance, epicardial coronary resistance, and end-diastolic resistance.
- Evaluation of myocardial contractile function, blood flow, and lactate production during sympathetic nerve stimulation and exercise.
Main Results:
- Nifedipine and felodipine effectively prevented alpha 1- and alpha 2-adrenoceptor-mediated increases in coronary resistance.
- Ca antagonists mitigated ischemic dysfunction and lactate production during sympathetic stimulation.
- Nifedipine improved myocardial blood flow and attenuated contractile dysfunction during exercise-induced ischemia in dogs with coronary stenosis.
- Beneficial effects were attributed to enhanced coronary dilator reserve, not reduced heart rate or afterload.
Conclusions:
- There is substantial experimental evidence supporting the functional antagonism of Ca antagonists against alpha-adrenergic coronary constriction.
- Ca antagonists can alleviate myocardial ischemia by counteracting alpha-adrenergic vasoconstriction.