Expression of inducible nitric oxide synthase, left ventricular function and remodeling in Dahl salt-sensitive hypertensive rats

Objective: Our aim was to examine whether inducible nitric oxide synthase (iNOS) expression in the left ventricle (LV) is associated with deterioration of contractility of the failing heart. Methods: Twenty male Dahl salt-resistant (DR) and 20 salt-sensitive (DS) rats were fed a high-salt diet starting at 6 weeks of age. Ten rats of each strain were studied at I I or 18 weeks of age. The blood pressure, heart rate and LV mass were measured. The indices of systolic function (contractility; E-cs) and diastolic function (stiffness; E-ed) were calculated from the end-systolic and end-diastolic pressure-volume relationships, respectively. The NOS mRNA and protein levels in the LV were determined by reverse transcription-polymerase chain reaction and Western blot analysis. Results: The blood pressure, heart rate and LV mass were greater in the DS rats than in DR rats (P<0.01, P<0.01, P<0.01). The E-es was greater in the DS rats than in DR rats at 11 weeks (3355+/-1048 vs. 2404+/-248 mmHg/ml; P<0.01), but it was smaller in the DS rats than in DR rats at 18 weeks (1424+/-375 vs. 2092+/-751 mmHg/ml; P<0.01). The E-cd was greater in DS rats than in DR rats at both ages. The NOS mRNA and protein levels were elevated in the 18-week-old DS rats (P<0.01, P<0.01) but not in the I I-week-old DS rats, in comparison with those in the DR rats. Conclusions: Cardiac NOS expression and nitric oxide production may have led to deterioration of systolic function from I I to 18 weeks. NOS may play an important role in the transition from compensated hypertrophy to failure. (C) 2003 Elsevier Ireland Ltd. All rights reserved.