The regression of chronic hypertrophy by a calcium channel antagonist and an ACE-inhibitor

Abstract

Hypertension is associated with a variety of morphological changes including left ventricular hypertrophy (LVH). The incidence of developing functional abnormalities 'are greatly increased for individuals with LVH [I]. Cardiac hypertrophy is induced by factors which initially stimulate protein synthesis rates, such as increased aortic pressure [2].Various calcium channel antagonists are currently available, for treating hypertension. However their lack of specificity and pharmacokinetic properties have led to the development of newer compounds. Amlodipine, a novel 1,4-dihydropyridine calcium channel antagonist possesses the desired feature of being administered once daily, due to its slow onset of action and long duration. Its mode of action in modulating cardiac protein synthesis is generally unknown. We therfore investigated (a) ventricular protein composition, and (b) protein synthesis rates, in spontaneously hypertensive rats treated with amlodipine. The effects of amlodipine were also compared with the angiotensin converting enzyme (ACE) inhibitor lisinopril. Male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto ( M Y ) rats were obtained at 15 weeks of age. Rats in the SHR groups had blood pressures within the range 175-190 mmHg. All rats were aged and weight matched from the start of the study. The rats were divided into the following designated groups (1) WKY, (control), treated with ordinary drinking water for 8 weeks.(2) WKY, treated with amlodipine in drinking water for 8 weeks.(3) WKY, treated with lisinopril in drinking water for 8 weeks.(4) SHR. (control), treated with ordinary drinking water for 8 weeks.( 5 ) SHR, treated with amlodipine in drinking water for 8 weeks.(6) SHR, treated with lisinopril in drinking water for 8 weeks.