Lee K C, Clas D M, Gorczyca W P, Silver P J, Ezrin A M
Department of Cardiovascular Pharmacology, Sterling Research Group, Rensselaer, NY 12144.
Drugs Exp Clin Res. 1991;17(7):323-36.
The cardiovascular and renal effects of graded i.v. dosages of two low Km cAMP cGMP-inhibitable (cGi) phosphodiesterase (PDE) inhibitors: CI-930 and milrinone (both 10-300 micrograms/kg), and three pure vasodilators: fenoldopam (0.1-3 micrograms/kg), Na nitroprusside (3-100 micrograms/kg) and hydralazine (0.1-3 mg/kg), were compared in conscious dogs. Mean arterial pressure was decreased by CI-930 at 0.3 mg/kg, milrinone at doses greater than or equal to 0.1 mg/kg (both by approximately -17 mmHg [max. change]), nitroprusside at doses greater than or equal to 0.01 mg/kg (-60 +/- 5 mmHg, [mean +/- SEM, max. change]), fenoldopam at doses greater than or equal to 0.001 mg/kg, and hydralazine at all doses (both by approximately -26 mmHg). Heart rate was increased by milrinone and CI-930 at dosages greater than or equal to 0.03 mg/kg (both by approximately 57 beats/min), nitroprusside and hydralazine at all dosages (54 +/- 18 and 91 +/- 18 beats/min, respectively) and fenoldopam at 3 micrograms/kg (21 +/- 2 beats/min). The cGi PDE inhibitors at 0.01-0.3 mg/kg and the pure vasodilators (except fenoldopam) at all dosages increased dP/dt (approximately 1500 and 900 mmHg/s, respectively). Milrinone (greater than or equal to 0.1 mg/kg), CI-930 (greater than or equal to 0.03 mg/kg), nitroprusside (greater than or equal to 0.01 mg/kg) and hydralazine (0.3-1 mg/kg) decreased left ventricular end diastolic pressure (all by approximately -4 mmHg). None of the agents adversely affected urinary volume, Na+ and K+ excretion rates. In conclusion, all agents (except fenoldopam) induced positive inotropic and chronotropic effects, and preload and afterload reduction. The cardiac effects of the pure vasodilators may be reflexly induced, whereas those of the cGi PDE inhibitors may be primarily due to inhibition of cardiac cGi PDE.
比较了两种低Km环磷酸腺苷-环磷酸鸟苷抑制型（cGi）磷酸二酯酶（PDE）抑制剂CI-930和米力农（静脉注射剂量均为10 - 300微克/千克）以及三种纯血管扩张剂非诺多泮（0.1 - 3微克/千克）、硝普钠（3 - 100微克/千克）和肼屈嗪（0.1 - 3毫克/千克）对清醒犬的心血管和肾脏的影响。CI-930剂量为0.3毫克/千克、米力农剂量大于或等于0.1毫克/千克（两者最大变化均约为-17 mmHg）、硝普钠剂量大于或等于0.01毫克/千克（-60±5 mmHg，[平均值±标准误，最大变化]）、非诺多泮剂量大于或等于0.001毫克/千克以及所有剂量的肼屈嗪（两者最大变化均约为-26 mmHg）时，平均动脉压降低。米力农和CI-930剂量大于或等于0.03毫克/千克（两者最大变化均约为57次/分钟）、所有剂量的硝普钠和肼屈嗪（分别为54±18次/分钟和91±18次/分钟）以及非诺多泮剂量为3微克/千克（21±2次/分钟）时，心率增加。0.01 - 0.3毫克/千克的cGi PDE抑制剂以及所有剂量的纯血管扩张剂（非诺多泮除外）均使dp/dt增加（分别约为1500和900 mmHg/s）。米力农（大于或等于0.1毫克/千克）、CI-930（大于或等于0.03毫克/千克）、硝普钠（大于或等于0.01毫克/千克）和肼屈嗪（0.3 - 1毫克/千克）使左心室舒张末期压力降低（均约为-4 mmHg）。所有药物（非诺多泮除外）均未对尿量、钠和钾排泄率产生不良影响。总之，所有药物（非诺多泮除外）均诱导正性肌力和变时作用，并降低前负荷和后负荷。纯血管扩张剂的心脏作用可能是反射性诱导的，而cGi PDE抑制剂的心脏作用可能主要是由于抑制心脏cGi PDE。
