EFFECTS OF THE DIHYDROPYRIDINE CALCIUM-CHANNEL BLOCKER AMLODIPINE ON VENTRICULAR AND ATRIAL PROTEIN-SYNTHESIS IN AN AORTIC CONSTRICTION MODEL OF HYPERTENSION AND, FOLLOWING CHRONIC TREATMENT, IN THE LEFT-VENTRICLE OF SHR RATS
Vb. Patel et al., EFFECTS OF THE DIHYDROPYRIDINE CALCIUM-CHANNEL BLOCKER AMLODIPINE ON VENTRICULAR AND ATRIAL PROTEIN-SYNTHESIS IN AN AORTIC CONSTRICTION MODEL OF HYPERTENSION AND, FOLLOWING CHRONIC TREATMENT, IN THE LEFT-VENTRICLE OF SHR RATS, International journal of cardiology, 58(3), 1997, pp. 241-255
The dihydropyridine calcium channel blocking agent amlodipine is an ef
fective anti-hypertensive agent and its use (in doses of 5 or 10 mg/da
y/kg body weight) was investigated in male Wistar rats with hypertensi
on induced by aortic constriction. Controls were sham-operated and pai
r-fed. At the end of the study, rates of protein synthesis were measur
ed with radiolabelled phenylalanine to calculate fractional rates of p
rotein synthesis (k(s)), absolute rates of protein synthesis (V-s) and
synthesis rates relative to RNA (k(RNA)). After 30 days of aortic con
striction, weights of the left ventricle and left atrium were signific
antly increased by hypertension. The weights of the right ventricle an
d right atrium were relatively unaffected. Hypertension was accompanie
d by significant increases in the protein and RNA contents of the left
ventricle and left atrium. The contractile and non-contractile protei
n contents were also increased in the left ventricles of hypertensive
rats as were total proteins and total RNA. In the myofibrillary fracti
on, k(s) decreased. The right ventricle and right atrium were generall
y unaffected except for a decline in mixed protein k(s). Many of these
changes in hypertension were ameliorated by treatment with amlodipine
, particularly at the higher dose (i.e. 10 mg/kg body weight/day) impl
icating an effect on protein metabolism. In the left ventricle these i
ncluded amelioration of the increases in mixed and contractile protein
s, total RNA contents; mixed V-s and V-s for sarcoplasmic and stromal
proteins. The ameliorating effects of amlodipine were moderate in the
left atrium. Furthermore, amlodipine also retarded the hyper tension-i
nduced reduction in right ventricule rates of protein synthesis. Altho
ugh the preceding study emphasises the preventative aspects of amlodip
ine's efficacy, an additional study was carried out in SHR rats to asc
ertain the applicability for regression per se. Amlodipine (10 mg/kg/b
ody weight) therapy for 30 weeks caused regression of LV mass, total p
rotein, RNA and DNA contents. We conclude that amlodipine, is an effic
ient agent in ameliorating the hypertension-induced changes in protein
metabolism in an aortic constriction model. Copyright (C) 1997 Elsevi
er Science Ireland Ltd.