INHIBITION OF BETA-MYOSIN HEAVY-CHAIN GENE-EXPRESSION IN PRESSURE-OVERLOAD RAT-HEART BY LOSARTAN AND CAPTOPRIL

AIM: To study the effects of losartan and captopril on beta-myosin hea vy chain (MHC), and alpha-MHC gene expression. METHODS: Pressure overl oad was produced by abdominal aortic coarctation (AAC) in rats. alpha- and beta-MHC mRNA were measured by Northern blot. RESULTS: In left ven tricular myocardium of sham-operated rats, the alpha-MHC mRNA predomin ated, while the beta-MHC mRNA was only detectable. In response AAC, th ere was a 70-fold increase in the beta-MHC mRNA (P<0.01), while alpha- MHC mRNA reduced to 26 % (P<0.01). Losartan (3 mg . kg(-1). d(-1), ig for 11 d) to AAC rats caused inhibitions of beta-MHC by 96 % and alpha -MHC by 86 % gene expression without lowering blood pressure. A reduct ion in beta-MHC mRNA was also seen in captopril-treated rats (30 mg . kg(-1). d(-1), ig for 11 d), but the inhibitory effect of captopril on alpha-MHC mRNA was less than that of losartan (44 % vs 86 %, P<0.05). CONCLUSION: The shift of MHC isoform induced by pressure overload is due to up-regulation of beta-MHC and down-regulation of alpha-MHC gene expression. Inhibition of beta-MHC gene expression by losartan is ach ieved primarily by direct blockade of angiotensin II type I receptors in the myocardium, independent on hemodynamics.