Neuronal Nitric Oxide Synthase and Neural growth factor interaction in the development of ventricular hypertrophy toward heart failure in the spontaneously hypertensive rats

Abstract

Ventricular hypertrophy (VH) is associated with an increased expression of neural growth factor (NGF) in spontaneously hypertension rats (SHR). In vitro studies suggest a strong interaction between NGF and neuronal nitric oxide synthase (nNOS), then in this study was determined the probable interaction between nNOS and NGF in the development of ventricular hypertrophy and heart failure in the SHR strain. Male Wistar Kyoto (WKY) and SHR strain at 2 and 8 months old were studied, and in accord with heart and ventricular weights and the presence of ventricular dilatation, SHR was classified as ventricular hypertrophy (SHR‐VH) and heart failure (SHR‐HF). Heart rate (HR), systolic arterial blood pressure (SABP), body, heart and ventricular weights, were analyzed. nNOS and NGF levels were measured in LV homogenates through Elisa assays, also nitrites levels in left ventricular homogenates were measured through Griess reaction in the experimental groups. The results show significantly differences between WKY and SHR strain in the parameters measured at 2 and 8 months old. HR, heart weight was significantly higher in SHR‐HF in comparison with WKY at the two edges studied. SABP was significantly different between WKY and SHRs, only at 8 months old. NGF in ng/ml, was increased in SHR‐LV at 2 and 8 months old (2.3±0.011, 2.6±0.017) whereas was reduced in SHR‐HF (1.43±0.015, 1.26±0.011) in comparison with the WKY (2.23±0.018, 1.89±0.015) P<0.05. The same pattern was observed with the nNOS levels in the experimental groups and was significantly different at 8 months old between experimental groups (nNOS in U/L; SHR‐VH‐64±6.9, SHR‐HF: 41±5 versus 54±3.5 in WKR) P<0.05. LV nitrites mean level in µM/L show a significantly increased in the experimental groups at 8 months old in comparison with the group at 2 months old (14.55±1.3 at 8 months against 4.3±0.88 at 2 months old, P<0.05). In conclusion the results shows that nNOS and NGF follows a similar pattern in the cardiac hypertrophy and heart failure, suggesting a positive interaction between them and that the preservation of nNOS and NGF production is associated to compensated ventricular hypertrophy, whereas reduced of them is associated to heart failure.