Effects of prazosin on coronary and left ventricular dynamics in conscious dogs

The left ventricular (LV) and coronary vascular effects of prazosin, a drug that reduces peripheral vascular resistance by blocking postsynaptic alpha receptors, were examined in conscious dogs. Prazosin, 0.07 mg/kg/min i.v. for 7 minutes, induced sustained hypotensive effects for more than 12 hours. The peak effects occurred 30-45 minutes after administration. Prazosin increased heart rate by 28 +/- 9%, did not change mean coronary blood flow significantly, decreased mean arterial pressure by 15 +/- 4%, LV end-diastolic diameter by 10 +/- 2%, LV end-systolic diameter by 8 +/- 2%, late diastolic coronary resistance by 22 +/- 7%, and LV dP/dt by 9 +/- 4%. These effects of prazosin were not altered substantially by maintaining heart rate constant with electrical pacing or by pretreatment with beta-adrenergic blockade. However, after chronic reserpine treatment, prazosin did not reduce either mean arterial pressure or late diastolic coronary resistance. The alpha-blocking properties of the drug were established when prazosin attenuated pressure responses to phenylephrine, norepinephrine and bilateral carotid occlusion. Thus, in conscious dogs with heart rate constant, prazosin, by blocking alpha-adrenergic receptors, induces prolonged coronary vasodilation associated with reductions in the major determinants of myocardial oxygen consumption, e.g., arterial and LV pressures, LV end-diastolic diameter and LV dP/dt. However, the coronary vasodilation was not intense enough to increase coronary blood flow above control levels.