Effect of antihypertensive therapy upon myosin isozyme distribution in spontaneously hypertensive rats.
BACKGROUND
Myosin isozymes have been known to become altered during the development and regression of myocardial hypertrophy, but the mechanism by which the shifting takes place is not known. The present paper describes the effects of antihypertensive drugs, with a known mechanism of action, upon myocardial mass, blood pressure and myosin isoforms in spontaneously hypertensive rats (SHR).


METHODS
SHR were treated with antihypertensive drugs and their blood pressure, myocardial mass and myosin isoforms determined.


RESULTS
A shift of myosin isoform from the V3 to the V1 type and normalization of myocardial hypertrophy were seen in rats treated with captopril but not in those treated with diuretics. Clonidine and guanethidine increased the V3 form in association with moderate control of blood pressure and no change in myocardial mass. Treatment with a beta-blocker regressed hypertrophy, controlled hypertension but increased the V3 form. Treatment with minoxidil normalized blood pressure, increased cardiac mass and increased the V3 type.


CONCLUSIONS
Treatment with different antihypertensive drugs does not cause similar types of shifts in myosin isoform and has divergent effects upon blood pressure and heart weight. Furthermore, there is no correlation between myocardial mass, blood pressure and myosin isozyme shifts. We conclude that factors other than blood pressure, myocardial mass and catecholamines modulate the shifting of myosin isoforms. Since captopril had a greater remedial effect upon myosin isoforms in our study than the more commonly used agents, we recommend that the current criteria for selection of antihypertensive drugs and the relation between those drugs and cardiac function be re-evaluated.
Sen
S
S
Department of Heart and Hypertension Research, Cleveland Clinic Foundation, Ohio 44195-5072.
Young
D
D
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D004591:Electrophoresis, Polyacrylamide Gel; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology; D009200:Myocardial Contraction / Q000187:drug effects; D009218:Myosins / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D002216:Captopril; D009218:Myosins