Attenuation of cardiac failure, dilatation, damage, and detrimental interstitial remodeling without regression of hypertrophy in hypertensive rats

Whether left ventricular (LV) hypertrophy is important in the development o f LV failure associated with advanced myocardial damage and detrimental cha mber and interstitial remodeling in hypertension has not been established. We examined the effect of an antihypertensive agent without the ability to regress LV hypertrophy on the development of LV changes in spontaneously hy pertensive rats (SHR). Hydralazine given to SHR from 5.2 to 26 months of ag e returned systolic blood pressure to Wistar Kyoto (WKY) control values but failed to prevent the increase in LV mass noted in SHR (at 26 months of ag e: WKY, 0.99 +/-0.02 g; untreated SHR, 1.40 +/-0.02 g; treated SHR, 1.36 +/ -0.02 g; P<0.001 in SHR versus WKY). In comparison to both 16-month-old SHR and age-matched WKY, 26-month-old untreated SHR developed signs consistent with heart failure, LV dilatation (an increased LV internal radius), an ec centric LV geometry, advanced myocyte necrosis, an increase in myocardial c ollagen solubility (an index of decreases in myocardial collagen cross-link ing), and marked increases in myocardial total, type III, and non-cross-lin ked myocardial collagen concentrations. Despite the inability of hydralazin e to regress LV hypertrophy, treated SHR did not develop signs of heart fai lure, myocyte necrosis, decreases in myocardial collagen cross-linking, or increases in myocardial total, type III, and non-cross-linked collagen at 2 6 months of age. Moreover, treatment attenuated the development of LV dilat ation and an eccentric LV geometry. In conclusion, antihypertensive therapy that does not attenuate LV hypertrophy but achieves normal blood pressure in SHR, is able to hinder the development of heart failure associated with advanced myocardial damage and detrimental chamber and interstitial remodel ing.