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

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Abstract
In conscious dogs the effects of .beta.-adrenergic receptor blockade was examined 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 .beta.1- and .beta.2-adrenergic receptor blockade) and atenolol (selective .beta.1-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 [change in pressure with time; 10 .+-. 1.8%). To determine whether the mechanism of coronary constriction involved the predominance of unopposed .alpha.-adrenergic receptor tone, the effects of propranolol and atenolol were examined in the presence of phentolamine (.alpha.1- and .alpha.2-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 .alpha.-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 cornary 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 .alpha.1-adrenergic receptor of phentolamine, but in spontaneous rhythm. In the presence of selective .alpha.1-adrenergic receptor bockade (prazosin), plasma catecholamines did not rise, and .beta.-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 .alpha.-adrenergic receptor blockade. Blockade of .beta.-adrenergic receptors elicits constriction of large coronary arteries in the conscious dog. This constriction is not diminished by .alpha.-adrenergic receptor blockade and is actually much greater after phentolamine, which blocks .alpha.1- and .alpha.2-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. A direct action of .beta.-adrenergic stimulation and blockade on the coronary vessels is not supported. The constriction appears related to the blockade of .beta.1-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 .alpha.-adrenergic receptor tone.