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 of LV failure associated with advanced myocardial damage and detrimental chamber 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 hypertensive rats (SHR). Hydralazine given to SHR from 5.2 to 26 months of age 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 age: 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 eccentric LV geometry, advanced myocyte necrosis, an increase in myocardial collagen solubility (an index of decreases in myocardial collagen cross-linking), and marked increases in myocardial total, type III, and non-cross-linked myocardial collagen concentrations. Despite the inability of hydralazine to regress LV hypertrophy, treated SHR did not develop signs of heart failure, myocyte necrosis, decreases in myocardial collagen cross-linking, or increases in myocardial total, type III, and non-cross-linked collagen at 26 months of age. Moreover, treatment attenuated the development of LV dilatation 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 remodeling.