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 myocardial structure and cardiac myosin isogene expression in pressure overload in rats were investigated. Portan rats were subjected to pressure overload by partial abdominal aortic constriction in order to study the effects of a 4-week treatment with hydralazine (15 mg/kg p.o.) on hemodynamics, ventricular structure, and ventricular total RNA, DNA, protein and myosin isoform expression pattern in sham (SO) and pressure-overloaded (p.o.) rats. P.o. increased the mean arterial pressure (MAP) and systolic blood pressure (SBP) and resulted in increased ventricular weight, LV wall thickness, total RNA and protein content; however, total DNA remained unchanged. The expression of fetal isogene beta-myosin heavy chain (beta-MHC) was markedly enhanced, whereas alpha-MHC was reduced. Hydralazine (15 mg/kg p.o.) normalized MAP and SBP, but did not modulate the hypertrophic changes of pressure-overloaded myocardium. It did not prevent an increase in ventricular total RNA and protein content and antithetical expression of myosin isoforms. Overall growth rate of rats was unaffected by hydralazine treatment. These results suggest that hydralazine has no direct effect in preventing the progression of cardiac hypertrophy and expression of beta-MHC, in spite of lowering blood pressure in pressure-overloaded rats. Thus, it further reaffirms that factors other than hemodynamics may play a pivotal role in the development of cardiac hypertrophy and induction of fetal isogene expression.
Reddy
D S
DS
Department of Pharmacology, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Singh
M
M
Ganguly
N K
NK
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D011506:Proteins; D014665:Vasodilator Agents; D006830:Hydralazine; D012313:RNA; D004247:DNA; D018995:Myosin Heavy Chains