EFFECTS OF LONG-TERM HYDRALAZINE TREATMENT ON MYOCARDIAL STRUCTURE AND EXPRESSION OF MYOSIN ISOGENES IN CARDIAC PRESSURE-OVERLOAD IN RATS

The long-term effects of an arterial vasodilator hydralazine, on myoca rdial structure and cardiac myosin isogene expression in pressure over load in rats were investigated. Portan rats were subjected to pressure overload by partial abdominal aortic constriction in order to study t he effects of a 4-week treatment with hydralazine (15 mg/kg p.o.) on h emodynamics, ventricular structure, and ventricular total RNA, DNA, pr otein and myosin isoform expression pattern in sham, (SO) and pressure -overloaded (PO) rats. PO increased the mean arterial pressure (MAP) a nd systolic blood pressure (SBP) and resulted in increased ventricular weight, LV wall thickness, total RNA and protein content; however; to tal DNA remained unchanged. The expression of fetal isogene beta-myosi n heavy chain (beta-MHC) was markedly enhanced whereas alpha-MHC was r educed. Hydralazine (15 mg/kg p.o.) normalized MAP and SBP but did not modulate the hypertrophic changes of pressure-overloaded myocardium I t did not prevent an increase in ventricular total RNA and protein con tent and antithetical expression of myosin isoforms. Overall growth ra re of rats was unaffected by hydralazine treatment. These results sugg est that hydralazine has no direct effect in preventing the progressio n of cardiac hypertrophy and expression of beta-MHC, in spite of lower ing blood pressure in pressure-overloaded rats. Thus, it further reaff irms that factors other than hemodynamics may play a pivotal role in t he development of cardiac hypertrophy and induction of fetal isogene e xpression.