Differential regulation of cardiac adrenomedullin and natriuretic peptide gene expression by AT(1) receptor antagonism and ACE inhibition in normotensive and hypertensive rats

Objective To study the effects of long-term treatment with the type 1 angio tensin (AT(1)) receptor antagonist losartan and the angiotensin-converting enzyme (ACE) inhibitor enalapril, on cardiac adrenomedullin (ADM), atrial n atriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expressi on. Methods Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats w ere given losartan (15 mg/kg per day) or enalapril (4 mg/kg per day) orally for in weeks. The effects of drugs on systolic blood pressure, cardiac hyp ertrophy, ANP, BNP and ADM mRNA and immunoreactive-ANP (IR)-ANP, IR-BNP and IR-ADM levels in the left ventricle and atria were compared. Results Losartan and enalapril treatments completely inhibited the increase of systolic blood pressure occurring with ageing in SHR, The ratio of hear t to body weight was reduced in both losartan- and enalapril-treated SHR an d WKY rats. Treatment with losartan or enalapril reduced left ventricular A NP mRNA and IR-ANP in both strains, and ventricular BNP mRNA levels in SHR rats, Inhibition of ACE, AT(1) receptor antagonism, changes in blood pressu re or cardiac mass had no effect on left ventricular ADM gene expression in SHR and WKY rats. In addition, atrial IR-ANP and IR-ADM levels increased i n SHR whereas IR-BNP levels decreased in WKY and SHR rats in response to dr ug treatments. Conclusions Our results show that ventricular ADM synthesis is an insensiti ve marker of changes in haemodynamic load or cardiac hypertrophy. Furthermo re, the expression of ADM, ANP and BNP genes is differently regulated both in the left ventricle and atria in response to AT(1) receptor antagonism an d ACE inhibition. (C) Lippincott Williams & Wilkins.