Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs.
The effects of three 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 three alpha-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by approximately 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 three 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 three 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 micrograms/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 less than 0.01) and prazosin (P less than 0.02). Thus the capacity of these three alpha-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous alpha-adrenergic-receptor agonists.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D010646:Phentolamine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D014665:Vasodilator Agents; C005185:trimazosin; D011224:Prazosin; D010646:Phentolamine