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 11 or 18 weeks of age. The blood pressure, heart rate and LV mass were measured. The indices of systolic function (contractility; E(es)) and diastolic function (stiffness; E(ed)) were calculated from the end-systolic and end-diastolic pressure-volume relationships, respectively. The iNOS 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(ed) was greater in DS rats than in DR rats at both ages. The iNOS mRNA and protein levels were elevated in the 18-week-old DS rats (P<0.01, P<0.01) but not in the 11-week-old DS rats, in comparison with those in the DR rats.

CONCLUSIONS

Cardiac iNOS expression and nitric oxide production may have led to deterioration of systolic function from 11 to 18 weeks. iNOS may play an important role in the transition from compensated hypertrophy to failure.