Exogenous nerve growth factor supplementation elevates myocardial immunoreactivity and attenuates cardiac remodeling in pressure-overload rats

Abstract

It is postulated that supplementation of exogenous nerve growth factor (NGF) might mediate improvement of the cardiac sympathetic nerve function in heart failure (HF). Local intramuscular injection of NGF near the cardiac sympathetic ganglia could influence the innervation pattern, norepinephrine transporter (NET) gene expression, and improve the cardiac remodeling in experimental HF animals. In this study, we injected NGF into the scalenus medius muscles of Sprague-Dawley rats with abdominal aortic constriction (AC). The nerve innervated pattern, left ventricular morphology, and function following injection in rats with AC were investigated respectively by immunohistochemistry and echocardiography. Levels of mRNA expression of NET, growth associated protein 43 (GAP 43), NGF and its receptors TrkA and p75(NTR), and brain natriuretic peptide (BNP) were measured by real-time polymerase chain reaction. The results showed that myocardial NGF mRNA levels were comparable in rats with AC. Short-term supplementation of exogenous NGF raised the myocardial NGF immunoreactivity, but did not cause hyperinnervation and NET mRNA upregulation in the AC rats. Furthermore, myocardial TrkA mRNA was found to be remarkably decreased and p75(NTR) mRNA was increased. Myocardial TrkA downregulation may play a beneficial effect for avoiding the hyperinnervation, and it is reasonable to postulate that p75(NTR) can function as an NGF receptor in the absence of TrkA. Interestingly, local NGF administration into the neck muscles near the ganglia could attenuate cardiac remodeling and downregulate BNP mRNA. These results suggest that exogenous NGF can reach the target tissue along the axons anterogradely, and improve the cardiac remodeling.