Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs

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Abstract
The effects of 3 .alpha.-adrenergic-receptor blocking agents (phentolamine, prazosin and trimazosin) were compared on the coronary circulation and left ventricular (LV) function in chronically instrumented conscious dogs. The 3 .alpha.-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by .apprx. 20%) and in the presence of .beta.-adrenergic-receptor blockade and constant heart rate. LV systolic pressure, LV end-diastolic pressure, and LV end-diastolic diameter also fell similarly with the 3 drugs. Phentolamine decreased the time rate of change of LV pressure (LV dP/dt) by 21 .+-. 3%, whereas trimazosin and prazosin decreased LV dP/dt only by 14 .+-. 2 and 11 .+-. 2%, respectively. LV velocity was not changed with trimazosin and prazosin but decreased with phentolamine by 12 .+-. 4%. The 3 drugs exerted differential effects on the coronary circulation. Only trimazosin increased coronary blood flow (18 .+-. 5%). Trimazosin decreased late diastolic coronary resistance (LDCR) by 35 .+-. 2%, which was significantly more than reductions in LDCR induced by prazosin (22 .+-. 2%) and by phentolamine (11 .+-. 3%). A test dose of phenylephrine (5.0 .mu.g/kg) increased mean arterial pressure by 53 .+-. 3.5 mmHg. After trimazosin, prazosin, and phentolamine, the same dose of phenylephrine increased mean arterial pressure by 24 .+-. 2.1, 14 .+-. 1.6 and 1.9 .+-. 0.6 mmHg, respectively. The response after phentolamine was significantly less than with trimazosin (P < 0.01) and prazosin (P < 0.02). The capacity of these 3 .alpha.-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous .alpha.-adrenergic-receptor agonists.