Mechanism of constriction of large coronary arteries by beta-adrenergic receptor blockade.

We examined in conscious dogs the effects of β-adrenergic receptor blockade on measurements of left circumflex coronary arterial diameter and blood flow and calculations of late diastolic coronary resistance and left circumflex coronary internal cross-sectional area. Propranolol (combined βi- and β2-adrenergjc receptor blockade) and atenolol (selective β2- adrenergic receptor blockade) elicited nearly identical effects. For example, propranolol and atenolol increased (P < 0.01) late diastolic coronary resistance by 13 ± 4.3 and 14 ± 3.0% and reduced (P < 0.01) large coronary cross-sectional area by 13 ± 1.5 and 12 ± 2.4%, respectively. This was associated with small reductions in heart rate (8 ± 2.0%) and left ventricular dP/dt (10 ± 1.8%). To determine whether the mechanism of coronary constriction involved the predominance of unopposed α-adrenergic receptor tone, the effects of propranolol and atenolol were examined in the presence of phentolamine (aj- and α2-adrenergic receptor blockade). Under these conditions plasma norepinephrine and epinephrine rose by 2114 ± 348 and 572 ± 139 pg/ml, respectively, and propranolol induced significantly greater (P < 0.01) increases in late diastolic coronary resistance (103 ± 23%) and decreases in large coronary cross-sectional area (25 ± 4.3%), heart rate (34 ± 3.8%) and left ventricular dP/dt (51 ± 4.3%), indicating that the mechanism probably did not involve α-adrenergic receptor activation. When heart rate was held constant, in the presence of phentolamine, propranolol elicited intermediate increases in late diastolic coronary resistance (39 ± 9.4%) and reductions in large coronary cross-sectional area (18 ± 3.6%) to those observed with propranolol in the presence and absence of phentolamine, but in spontaneous rhythm. In the presence of selective α1-adrenergic receptor blockade (prazosin), plasma catechol- amines did not rise, and β-adrenergic receptor blockade induced similar increases in late diastolic coronary resistance (15 ± 3.7%) and decreases in large coronary cross-sectional area (14 ± 4.0%) and left ventricular dP/dt (12 ± 2.4%), as observed in the absence of α-adrenergic receptor blockade. Thus, blockade of β-adrenergic receptors elicits constriction of large coronary arteries in the conscious dog. This constriction is not diminished by α-adrenergic receptor blockade and is actually much greater after phentolamine, which blocks a]- and α2-adrenergic receptors, and elevates levels of catecholamines and, consequently, heart rate and myocardial contractility. The changes in coronary vasomotor tone were not accompanied by changes in A-VO2 difference. These experiments do not support a direct action of β-adrenergic stimulation and blockade on the coronary vessels. Thus, the constriction appears related to the blockade of β-adrenergic effects on heart rate and left ventricular dP/dt, i.e., those factors that alter myocardial metabolic demands and coronary blood flow, but does not appear to involve the predominance of unopposed αadrenergic receptor tone.