Chronic N-G-nitro-L-arginine methyl ester-induced hypertension - Novel molecular adaptation to systolic load in absence of hypertrophy

Background-Chronic N-G-nitro-L-arginine methyl ester (L-NAME), which inhibi ts nitric oxide synthesis, causes hypertension and would therefore be expec ted to induce robust cardiac hypertrophy. However, L-NAME has negative meta bolic effects on protein synthesis that suppress the increase in left ventr icular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that ada ptation to pressure overload occurs even when hypertrophy is suppressed. Methods and Results-Male rats received L-NAME (50 mg . kg(-1) . d(-1)) or n o drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of sys tolic wall stress similar to those of rats with aortic stenosis (85 +/- 19 versus 92 +/- 16 kdyne/cm). Rats with aortic stenosis developed a nearly 2- fold increase in LV mass compared with controls. Tn contrast, in the L-NAME rats, no increase in LV mass (1.00 +/- 0.03 versus 1.04 +/- 0.04g) or hype rtrophy of isolated myocytes occurred (3586 +/- 129 versus 3756 +/- 135 mu m(2)) compared with controls. Nevertheless, chronic pressure overload was n ot accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium- dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca2+ ATPase (SERCA-2). Conclusions-When the expected compensatory hypertrophic response is suppres sed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.