Alteration of cardiac collagen phenotypes in hypertensive hypertrophy: role of blood pressure.
The myocardium contains a fibrillar collagen matrix that consists primarily of type I and type III collagens. There is a marked alteration in the ratio and amount of collagen phenotypes in myocardial hypertrophy due to pressure overload. The purpose of the present study is (1) to study the effect of antihypertensive therapy on collagen phenotypes, if instituted before development of hypertension in spontaneously hypertensive rat (SHR), and continued into adult life and (2) to study the effects of dissociation of hypertension from hypertrophy, on collagen phenotypes in SHRs. The present study shows the effect of two antihypertensive drugs, hydralazine and captopril, on collagen phenotypes in SHRs. Both hydralazine and captopril effectively controlled blood pressure in SHRs, but only captopril regressed hypertrophy and corrected the altered distribution of myocardial collagen phenotypes I and III. Untreated SHRs had a collagen type I:III ratio of 10.19 +/- 0.27, compared with that of 6.41 +/- 0.30 in normotensive WKY (P < 0.001). Captopril-treated SHRs had a collagen type I:III ratio of 6.75 +/- 0.37, which did not differ significantly from that in normotensive WKY. Hydralazine-treated SHRs had a collagen I:III ratio of 10.07 +/- 0.39, which is similar to the ratio in untreated SHRs. In normotensive rats, neither captopril nor hydralazine significantly altered collagen content or the ratio of type I:III collagen. Thus captopril, an angiotensin converting enzyme inhibitor, not only regressed hypertrophy but also reversed the altered distribution of type I and type III collagen whereas hydralazine which effectively controlled blood pressure, did not regress hypertrophy and did not correct the altered distribution in collagen phenotypes. These studies suggest that alteration of collagen phenotypes during hypertensive hypertrophy is independent of blood pressure control and myocardial mass.
Mukherjee
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Department of Heart and Hypertension Research, Cleveland Clinic Foundation, OH 44195-5071.
Sen
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics*; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D006830:Hydralazine; D003094:Collagen; D002216:Captopril