ROLE OF ALPHA(2)-ADRENOCEPTORS IN NORMAL AND ATHEROSCLEROTIC HUMAN CORONARY CIRCULATION

Background. Experimental studies on the effects of alpha2-adrenoceptors on regional coronary blood flow in normal and ischemic myocardium are highly controversial. A beneficial effect on regional ischemic myocardium has been demonstrated in different animal preparations with either alpha2-adrenoceptor blockade or stimulation. Animal studies also demonstrated that postsynaptic alpha2-adrenoceptors mediate vasoconstriction in coronary and femoral vascular beds. The aims of the study were 1) to investigate the effects of regional alpha2-adrenoceptor stimulation on regional coronary blood flow in subjects with angiographically normal coronary arteries, 2) to assess the effect of alpha2-adrenoceptor blockade on coronary circulation in control subjects, and 3) to examine the influence of atherosclerosis on coronary blood flow response to alpha2-adrenoceptor blockade. Methods and Results. The effect of regional administration of BHT 933 (a selective alpha2-adrenoceptor agonist) was studied in eight subjects with angiographically normal coronary arteries. The coronary blood flow velocity was measured using a subselective intracoronary 3F Doppler catheter and coronary diameter by quantitative coronary angiography. BHT 933 induced a reduction in coronary artery diameter from 2.5+/-0.6 mm to 1.8+/-0.4 mm (p<0.05) as well as in coronary blood flow velocity (from 6.4+/-0.9 cm/sec to 4.6+/-1.9 cm/sec, p<0.01). In some subjects, ST segment abnormalities occurred. In patients with angiographically normal coronary arteries (n=6), the regional infusion of a selective alpha2-adrenoceptor blocking agent after beta-blockade did not change coronary diameter or coronary blood How velocity. In contrast, in patients with significant coronary stenoses (n=6), regional infusion of an alpha2-adrenoceptor blocking agent reduced regional coronary artery diameter (from 2.3+/-0.5 mm to 2.1+/-O.6 mm, p<0.01) as well as coronary blood flow velocity (from 5.8+/-0.8 cm/sec to 3.7+/-0.6 cm/sec, p<0.05); in addition, alpha2-adrenoceptor blockade significantly increased coronary sinus plasma norepinephrine levels (from 300+/-144 pg/ml to 429+/-207 pg/ml, p<0.01). Conclusions. The selective in vivo stimulation of alpha2-adrenoceptors produces a reduction in coronary blood flow and diameter in humans with angiographically normal coronary arteries. alpha2-Adrenergic blockade does not change coronary blood How in subjects with angiographically normal coronary arteries (suggesting no resting alpha2-adrenergic vasoconstrictor tone), whereas in patients with coronary artery stenosis, regional coronary blood flow decreases after alpha2-receptor blockade. Finally, our data also suggest that alpha2-adrenoceptors participate in the modulation of sympathetic neuronal norepinephrine release in the human heart.