Felodipine prevents the poststenotic myocardial ischemia induced by alpha 2-adrenergic coronary constriction.
Alpha 2-adrenoceptor-mediated coronary constriction contributes to the precipitation of myocardial ischemia during sympathetic activation. Felodipine is a novel dihydropyridine calcium-channel antagonist with vascular selectivity. In this study, the effect of felodipine on alpha 2-adrenoceptor-mediated poststenotic coronary constriction was investigated. In ten open-chest dogs, the selective alpha 2-adrenoceptor agonist BHT 933 (200 micrograms IC) was infused before and after production of a severe stenosis on the left circumflex coronary artery. BHT 933 increased calculated resistance of the intact left circumflex coronary artery from 1.16 +/- 0.30 (SD) to 2.00 +/- 0.70 mmHg*min*100 g/ml (p less than 0.05) without changing posterior systolic wall thickening (sonomicrometry) (14.2 +/- 2.8% vs. 14.1 +/- 2.7%). In the presence of a severe stenosis, BHT 933 increased poststenotic coronary resistance from 1.59 +/- 0.54 to 2.88 +/- 1.16 mmHg*min*100 g/ml (p less than 0.05) and decreased posterior systolic wall thickening from 11.9 +/- 2.7% to 8.2 +/- 3.1% (p less than 0.05). In contrast, after intravenous pretreatment with felodipine (4 micrograms/kg), intracoronary infusion of BHT 933 did not change coronary resistance (1.69 +/- 0.61 vs. 1.61 +/- 0.64 mmHg*min*100 g/ml) and posterior systolic wall thickening (12.1 +/- 3.0% vs. 12.6 +/- 2.9%). In conclusion, felodipine prevents alpha 2-adrenoceptor-mediated coronary constriction and ischemic regional myocardial dysfunction distal to a severe coronary stenosis.
Ehring
T
T
Abteilung für Pathophysiologie, Universitätsklinikum Essen, FRG.
Heusch
G
G
D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors*; D000818:Animals; D001381:Azepines / Q000037:antagonists & inhibitors*; D003251:Constriction, Pathologic; D003327:Coronary Disease / Q000139:chemically induced / Q000517:prevention & control*; D004285:Dogs; D015736:Felodipine / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D014662:Vasoconstrictor Agents; C015603:azepexole; D015736:Felodipine