Nakai M, Matsui Y, Yamamoto J
Arch Int Pharmacodyn Ther. 1986 Feb;279(2):291-303.
Experiments were conducted on 53 conscious young male spontaneously hypertensive rats utilizing radiolabeled microspheres to analyze the acute and chronic hemodynamic effects of a newly synthesized antihypertensive drug, E614. The hemodynamic variables were observed on the 1st and 6th days of E614 treatment (p.o., once daily) in separate groups of rats. When the drug was given at a smaller dose (10 mg/kg body weight) over 6 days, the hypotensive action of E614 was found to be due mainly to a reduction of the total peripheral vascular resistance with no significant change in the cardiac output (CO). A supra-pharmacological dose (100 mg/kg), however, lowered the mean arterial pressure (AP) due mainly to a significant reduction of the CO in both the acute and chronic treatments. We found little influence of the drug on heart rate, and the coronary and renal vascular beds in any of the present experimental settings. The cerebral blood flow appeared not to change significantly unless the AP fell to such an extent that a fall in cerebral blood flow took place despite the autoregulatory mechanism of the brain blood vessels. The tissue perfusion was also well preserved in the gastrointestinal tract.
利用放射性微球对53只清醒的雄性自发性高血压幼鼠进行实验，以分析一种新合成的抗高血压药物E614的急性和慢性血流动力学效应。在E614治疗的第1天和第6天（口服，每日一次），对不同组的大鼠观察血流动力学变量。当以较小剂量（10毫克/千克体重）给药6天时，发现E614的降压作用主要是由于总外周血管阻力降低，心输出量（CO）无显著变化。然而，超药理剂量（100毫克/千克）在急性和慢性治疗中均主要通过显著降低CO来降低平均动脉压（AP）。在目前任何实验设置中，我们发现该药物对心率以及冠状动脉和肾血管床几乎没有影响。除非AP下降到尽管脑血管有自动调节机制但脑血流量仍会下降的程度，否则脑血流量似乎不会有显著变化。胃肠道的组织灌注也保存良好。
