Clapham J C, Buckingham R E
Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, U.K.
J Cardiovasc Pharmacol. 1988;12(5):555-61. doi: 10.1097/00005344-198811000-00009.
The haemodynamic profile of the novel antihypertensive agent, cromakalim (BRL 34915), has been studied in conscious and anaesthetised cats. Given orally (0.03 and 0.06 mg/kg) to conscious cats and by intravenous infusion (0.002 mg/kg/min for 7-10 min) to anaesthetised animals, cromakalim reduced arterial pressure (AP; systolic/diastolic) and total peripheral resistance (TPR) while increasing cardiac output (CO) via both its components [heart rate (HR) and stroke volume (SV)]. In both models, HR changes were minimal for reductions of AP approaching 20 mm Hg. In a second group of conscious cats, cromakalim increased mean renal blood flow (MRBF) at hypotensive doses (0.03 and 0.06 mg/kg orally); HR was only significantly raised following the higher dose of cromakalim. In anaesthetised animals, intravenously infused cromakalim had little effect on central venous pressure and increased cardiac contractility. The data indicate that cromakalim lowers AP by reducing TPR with minimal increase in HR. In addition, cromakalim has a potentially beneficial effect on MRBF.
新型抗高血压药物克罗卡林（BRL 34915）的血流动力学特征已在清醒和麻醉猫身上进行了研究。给清醒猫口服（0.03和0.06毫克/千克），给麻醉动物静脉输注（0.002毫克/千克/分钟，持续7 - 10分钟），克罗卡林降低动脉压（AP；收缩压/舒张压）和总外周阻力（TPR），同时通过其两个组成部分[心率（HR）和每搏输出量（SV）]增加心输出量（CO）。在两种模型中，当AP降低接近20毫米汞柱时，HR变化最小。在第二组清醒猫中，克罗卡林在降压剂量（口服0.03和0.06毫克/千克）下增加平均肾血流量（MRBF）；仅在给予较高剂量的克罗卡林后HR才显著升高。在麻醉动物中，静脉输注克罗卡林对中心静脉压影响很小，并增加心脏收缩力。数据表明，克罗卡林通过降低TPR降低AP，同时HR升高最小。此外，克罗卡林对MRBF有潜在的有益作用。
