Osborne M W, Wenger J J, Zanko M T
J Pharmacol Exp Ther. 1977 Jan;200(1):195-206.
Ro 2-2985 increased mean arterial blood pressure in both the venous bypass preparation and the intact animal; however, total peripheral resistance increased in the venous bypass preparation with a constant cardiac output but decreased in the intact animal with an increase in cardiac output. These observations indicate a drug-related increase in the distensibility of the aorta at the same arterial pressure. In vivo ventricular function curves were shifted to the left indicating enhanced myocardial performance with the translocation of large volumes of blood to the central circulation since total body venous compliance was significantly decreased. Beta adrenergic blocking doses of propranolol blocked the positive inotropic effect of Ro 2-2985 while myocardial depression produced by toxic doses of propranolol was reversed. This observation suggests several mechanisms for the Ro 2-2985 metabolic mediation of myocardial muscle contraction. The cardiovascular effects produced by Ro 2-2985 were accompanied by a marked polycythemia and a decrease in plasma volume without a change in total circulating blood volume, while blood glucose values showed a nonsignificant increase. Ro 2-2985 produced a marked increase in cardiac output. The increase in myocardial performance appears to be complex since myocardial force of contraction, dT/dt, dP/dt:P40 and Vmax were all increased. RO 2-2985 increased coronary flow without an increase in resistance. There were no significant increases in myocardial arteriovenous glucose, lactate, K+, Ca++, Na+ or Cl.
Ro 2-2985可使静脉搭桥制备模型和完整动物的平均动脉血压升高；然而，在静脉搭桥制备模型中，总外周阻力升高而心输出量恒定，在完整动物中，总外周阻力降低而心输出量增加。这些观察结果表明，在相同动脉压下，该药可使主动脉的扩张性增加。体内心室功能曲线向左移位，表明心肌性能增强，大量血液转移至体循环中心，因为全身静脉顺应性显著降低。β肾上腺素能阻断剂量的普萘洛尔可阻断Ro 2-2985的正性肌力作用，而中毒剂量的普萘洛尔所产生的心肌抑制作用可被逆转。这一观察结果提示了Ro 2-2985对心肌收缩进行代谢调节的几种机制。Ro 2-2985所产生的心血管效应伴有明显的红细胞增多症和血浆量减少，而总循环血量无变化，同时血糖值有不显著升高。Ro 2-2985可使心输出量显著增加。心肌性能的增加似乎很复杂，因为心肌收缩力、dT/dt、dP/dt:P40和Vmax均增加。Ro 2-2985可增加冠脉流量而不增加阻力。心肌动静脉葡萄糖、乳酸、K+、Ca++、Na+或Cl均无显著增加。
