Normalisation of blood pressure in hypertensive TGR(mREN2)27 rats by amlodipine vs. enalapril: effects on cardiac hypertrophy and signal transductionpathways

It is still a controversial issue whether different classes of antihyperten sive drugs are equally effective in the regression of cardiac hypertrophy a nd associated complications. The present study compared the effects of prol onged treatment with the Ca2+-channel blocker amlodipine and the ACE inhibi tor enalapril, respectively, in TGR(mREN2)27 rats (TGR), an animal model of renin-dependent hypertension. TGR were divided into three groups and received either amlodipine, enalapri l or drinking water without addition, Sprague-Dawley rats (SPRD) served as normotensive control group. Cardiovascular parameters were monitored by rad iotelemetry, and drug doses were titrated until 24-h blood pressure was red uced to approximately 140/90 mmHg in both active treatment groups. After 8 weeks of treatment left ventricular (LV) hypertrophy was completely reversed in both treatment groups despite a tenfold increase in plasma ang iotensin II in amlodipine-treated TGR. In untreated TGR LV catecholamines w ere depleted, and beta (1)-adrenergic stimulation of adenylyl cyclase was b lunted. Treatment of TGR with enalapril prevented both the depletion of tis sue catecholamines and the desensitisation of LV beta (1)-adrenoceptors. Am lodipine had no effect on cardiac adrenergic signal transduction. Basal act ivity of LV soluble guanylyl cyclase was not different between TGR and SPRD , but its sensitivity to stimulation by nitric oxide was slightly reduced i n TGR. Treatment had no effect on basal and stimulated guanylyl cyclase act ivity. The present study in an animal model of renin-dependent hypertension suggests that blood pressure reduction per se is sufficient for a regressi on of cardiac hypertrophy. However, beta -adrenergic desensitisation was pr evented only in the enalapril-treated group, supporting a blood pressure-in dependent contribution of the renin-angiotensin system to the regulation of beta -adrenergic signal transduction.