Macho P, Hintze T H, Vatner S F
Am J Physiol. 1982 Jul;243(1):H94-8. doi: 10.1152/ajpheart.1982.243.1.H94.
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.
在长期植入仪器的清醒犬中，比较了三种α-肾上腺素能受体阻滞剂（酚妥拉明、哌唑嗪和曲马唑嗪）对冠脉循环和左心室（LV）功能的影响。三种α-肾上腺素能受体阻滞剂以等效降压剂量给药（平均动脉压下降约20%），且处于β-肾上腺素能受体阻断和心率恒定的状态。三种药物使左心室收缩压、左心室舒张末期压力和左心室舒张末期直径也出现类似下降。酚妥拉明使左心室压力变化率（LV dP/dt）降低21±3%，而曲马唑嗪和哌唑嗪仅使LV dP/dt分别降低14±2%和11±2%。曲马唑嗪和哌唑嗪对左心室速度无影响，但酚妥拉明使其降低12±4%。三种药物对冠脉循环产生不同影响。仅曲马唑嗪增加冠脉血流量（18±5%）。曲马唑嗪使舒张末期冠脉阻力（LDCR）降低35±2%，显著大于哌唑嗪（22±2%）和酚妥拉明（11±3%）引起的LDCR降低。一剂苯肾上腺素（5.0微克/千克）使平均动脉压升高53±3.5毫米汞柱。给予曲马唑嗪（trimazosin）、哌唑嗪和酚妥拉明后，相同剂量的苯肾上腺素分别使平均动脉压升高24±2.1、14±1.6和1.9±0.6毫米汞柱。酚妥拉明后的反应明显小于曲马唑嗪（P<0.01）和哌唑嗪（P<0.02）。因此，这三种α-肾上腺素能受体阻断药物扩张冠脉血管的能力与其阻断外源性α-肾上腺素能受体激动剂的能力成反比。
