α1 and α2-Adrenoceptor-Mediated Vasoconstriction of Large and Small Canine Coronary Arteries In Vivo

Abstract

.alpha.-Adrenoceptor subtypes mediating vasoconstriction of large epicardial and small resistive coronary arteries was investigated in 26 open-chest dogs. The left circumflex coronary artery was perfused at a constant pressure. Large vessel vasomotion was determined by measurement of circumflex coronary arterial diameter (ultrasonic transit-time technique); the vasomotion of the small resistive coronary arteries was determined from calculated end-diastolic circumflex artery resistance. .beta.-Receptors were blocked by propranolol (2 mg/kg i.v.) and both vagal nerves were cut. In 8 dogs, the intracoronary administration of the .alpha.1-adrenoceptor agonist methoxamine (500 .mu.g) increased calculated large vessel resistance by 18.8 .+-. 5.7% and enddiastlic resistance by 9.5 .+-. 0.3%. Intracoronary .alpha.2-adrenoceptor agonist BHT 920 (500 .mu.g) administration did not affect large vessel resistance, but increased end-diastolic resistance by 37.5 .+-. 5.6%. In an additional 18 dogs, left cardiac sympathetic nerve stimulation induced an increase in large vessel resistance by 11.1 .+-. 0.9% and in end-diastolic resistance by 31.8 .+-. 3.0%. The large vessel resistance increase was prevented by the .alpha.1-adrenoceptor antagonist prazosin (1.2 mg/kg i.v.) which still permitted an increase in end-diastolic resistance by 23.0 .+-. 3.2%. The increase in enddiastolic resistance was prevented by the .alpha.2-adrenoceptor antagonist rauwolscine (0.2 mg/kg i.v.) which still permitted an increase in large vessel resistance by 11.9 .+-. 2.4%. The Ca antagonist nifedipine (20 .mu.g/kg i.v.) prevented an increase in large vessel resistance by 11.9 .+-. 2.4%. The Ca antagonist nifedipine (20 .mu.g/kg i.v.) prevented an increase in large vessel resistance and in end-diastolic resistance during sympathetic stimulation. .alpha.-Adrenoceptor-mediated vasoconstriction of large coronary arteries is apparently mediated exclusively by .alpha.1-adrenoceptors; .alpha.-adrenergic vasoconstriction of small resistive coronary arteries is mediated in part by .alpha.1-, but mostly by .alpha.2-adrenoceptors. The Ca antagonist nifedipine can antagonize the vasoconstriction initiated by .alpha.1- and .alpha.2-adrenoceptors.