Selective effects of alpha-methyldopa on myocardial cell components independent of cell size in normotensive and genetically hypertensive rats.
Alpha methyldopa has been shown to modify left ventricular mass and normalize mitochondria/myofibrils volume ratio in spontaneously hypertensive rats (SHR) when administered during the stage of developing cardiac hypertrophy (Tomanek et al., Cardiovas Res 23: 173, 1979). To evaluate the long-term effects of this antihypertensive agent, the drug was administered to SHR and normotensive (WKY) rats between the ages of 1 and 12 months. In another group of SHR and WKY, treatment was delayed until the age of 12 months and the animals were then treated for 3 months. Treatment with alpha-methyldopa had similar effects on systolic blood pressures in both SHR groups; group means (+/- SEM) were 151 +/- 1 in the long-term treatment group and 157 +/- 5 in the delayed treatment group compared to 178 +/- 4 and 176 +/- 3 for their respective controls. While left ventricular weight and cell size were significantly lower after early long-term treatment (compared to nontreated SHR), delayed treatment had no significant effect on these indices of left ventricular mass. Despite the effectiveness of early long-term treatment in modifying left ventricular mass, the relative volumes of mitochondria and myofibrils, as well as other cellular components (sarcoplasm), were not altered. In contrast, delayed treatment caused a significant increase (approximately twofold) in relative sarcoplasmic volume and a decrease in relative myofibrillar volume in both SHR and WKY. These findings indicate that shifts in the relative volumes of intracellular components after alpha-methyldopa are independent of cell size and blood pressure. Furthermore, the data suggest that the effects of alpha-methyldopa on the myocardial cell are dependent on or influenced by factors associated with the development or stabilization of hypertrophy and/or age.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D002451:Cell Compartmentation / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008750:Methyldopa / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D006830:Hydralazine; D008750:Methyldopa; D002216:Captopril