Left ventricular adaptation to chronic pressure overload induced by inhibition of nitric oxide synthase in rats

Summary

Recent studies have indicated that chronic inhibition of nitric oxide synthase induces arterial hypertension without myocardial hypertrophy. We investigated the mechanisms of left ventricular (LV) adaptation to this condition, Also, we analyzed the effect of the angiotensin-converting enzyme inhibitor (ACEI), lisinopril, in this experimental model of ventricular pressure overload. Fiftyeight Wistar rats received eight weeks of treatment with either N^w-nitro-L-arginine-methyl ester (L-NAME group, n=19), lisinopril (LISINOPRIL group, n=19) or the combination of both drugs (LNAMELIS group, n=20). All results were compared to age and sex matched untreated rats (CONTROL group, n=18). Tail-cuff blood pressure rose significantly in L-NAME treated rats (195±29 mm Hg) compared to the CONTROL (141±12 mm Hg), LISINOPRIL (97±13 mm Hg), and LNAMELIS (113±16 mm Hg) groups. There was no myocardial hypertrophy in the chronically hypertensive rats. The ventricular unstressed volume was significantly reduced in the L-NAME group (0.119±0.027 mL) compared to the CONTROL (0.158±0.026 mL) indicating a disproportional reduction in ventricular volume related to the myocardial mass. The chamber size modification resulted in a systolic stress which was comparable to the CONTROL even though the isovolumetric systolic pressure was higher. The systolic functional data indicated preserved myocardial contractility in L-NAME. LV compliance was increased in the LISINOPRIL group and myocardial passive stiffness was lower in all treated rats compared to CONTROL. We conclude that LV adaptation to chronic pressure overload without hypertrophy involves changes in chamber geometry and myocardial diastolic mechanical properties. Also, ACEI fully prevents L-NAME induced hypertension, reduces myocyte cross-sectional area, and myocardial passive stiffness. The combination of L-NAME plus lisinopril decreases the load independent index of myocardial contractility.