Effect of heart failure on number of NADPH-diaphorase (nNOS) positive neurons in hypothalamus of rats

We have shown a decreased neuronal nitric oxide synthase (nNOS) message in the hypothalamus of rats with heart failure (HF). The purpose of this study was to determine changes in NADPH-diaphorase (commonly used marker for neuronal NOS activity) positive neurons in specific hypothalamic sites of rats with HF. After a standard histochemical protocol, nNOS positive neurons were measured in paraventricular nucleus (PVN), supraoptic nucleus (SON), median preoptic area (MPO), subfomical organ (SFO), organum vasculosum of the lamina terminalis (OVLT) and lateral hypothalamus (LH) of coronary artery ligated rats (HF group; n=8) and sham operated control rats (n=9). The rats in HF group displayed infarcts greater than 35% of the left ventricular wall, 16 weeks after coronary artery ligation. Sham rats had no observable damage to the myocardium. Heart failure rats had a significantly lower number of nNOS positive cells in PVN (36% less) compared to sham rats. The number of nNOS positive cells remained unaltered in SON, MPO and LH in rats with HF. Conversely there were increased number of nNOS positive cells in the SFO (42% greater) and OVTL (100% greater) in HF rats. This study demonstrates that; 1) there is decreased neuronal NOS activity in PVN as measured by expression of diaphorase staining in rats with heart failure, and 2) there was increase in nNOS positive ceils in the SFO and OVLT of rats with HF. These data support the concluslor that NO system within hypothalamic areas involved in controlling autonomic outflow are altered during heart failure and may contribute to the elevated levels of vasopressin and sympatho-excitation commonly observed in HF.