Comparative study of the antihypertensive and metabolic effects of the angiotensin II antagonist valsartan versus captopril in rats

ABSTRACT

Angiotensin II is a key hormone of the renin-angiotensin system which regulates blood pressure. Valsartan is a highly selective and specific direct angiotensin II antagonist. It inhibits angiotensin II binding to the angiotensin II receptor subtype ATI and blocks the pressor effect of angiotensin II in a dose-dependent manner. This study was conducted to evaluate the antihypertensive effect of valsartan comparing it to the converting enzyme inhibitor captopril, as well as their effect on glucose and insulin levels in blood of fasting rats. 70 adult albino rats were used in this study. Captopril and valsartan were given to 2 groups of rats [each of 10 rats] in a dose of 3 mg/kg orally daily for 3 weeks to study their effect on serum glucose and insulin levels in normal fasting adult rats .It was found that captopril significantly decreased serum glucose values from 91.4 [3.92 to 75.9 [0.48 [p<0.05]; while it significantly increased serum insulin values from 11.45 [1.2 to 15.97[0.48 [p< 0.05]. On the other hand, valsartan induced insignificant changes in either glucose or insulin values. It was found that valsartan has approximately an equipotent antihypertensive effect compared to captopril in the 2-kidney-One clip adult hypertensive rats, when given daily orally for 4 weeks. Captopril significantly decreased the systolic blood pressure from 167.7[3.4 to 140.9 [2.7 with 15.98% reduction [P< 0.001] by the end of the 4th week; while valsartan also significantly decreased the systolic blood pressure from 166.54.2 to 145.62.5 [p< 0.001] with 12.55% reduction at the end of the 4th week. In renal hypertensive rats [2K-IC] pretreated by hydrochlorothiazide [2.25mg/kg b.w.] orally daily for 3weeks, captopril induced a sharp significant drop of blood pressure when given orally as a single dose [5mg/kg b.w.] especially in the first hour, from 148.3[2.1 to 132.7[3.1 with 10.5% reduction [p< 0.001]. On time other hand. valsartan, induced a slow non-significant fall of blood pressure after the same period with the same dose and route of administration, from 147.9[3.1 to 141.7[3.2 with 4.19% reduction, [p> 0.05]. It is concluded that valsartan could replace angiotensin converting enzyme inhibitors in patients who are liable to suffer from angioedema or could not tolerate dry persistent cough Associated with, the increase of bradykinin and prostaglandin levels following ACEIs administration. The lack of time first dose phenomenon as reported by this investigation, could be an added advantage of valsartan over captopril. Also, because at the lack of adverse metabolic effects on glucose tolerance valsartan could prove to be the second choice drug in diabetic hypertensive patients who could not tolerate ACEIs