Abstract
Renal denervation (RDN) has been shown to restore endogenous neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) and reduce sympathetic drive during chronic heart failure (CHF). The purpose of the present study was to assess the contribution of afferent renal nerves to the nNOS-mediated sympathetic outflow within the PVN in rats with CHF. CHF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, selective afferent RDN (A-RDN) was performed by bilateral perivascular application of capsaicin on the renal arteries. Seven days after intervention, nNOS protein expression, nNOS immunostaining signaling, and diaphorase-positive stained cells were significantly decreased in the PVN of CHF rats, changes that were reversed by A-RDN. A-RDN reduced basal lumbar sympathetic nerve activity in rats with CHF (8.5%±0.5% versus 17.0%±1.2% of max). Microinjection of nNOS inhibitor L-NMMA (L-N(G)-monomethyl arginine citrate) into the PVN produced a blunted increase in lumbar sympathetic nerve activity in rats with CHF. This response was significantly improved after A-RDN (Δ lumbar sympathetic nerve activity: 25.7%±2.4% versus 11.2%±0.9%). Resting afferent renal nerves activity was substantially increased in CHF compared with sham rats (56.3%±2.4% versus 33.0%±4.7%). These results suggest that intact afferent renal nerves contribute to the reduction of nNOS in the PVN. A-RDN restores nNOS and thus attenuates the sympathoexcitation. Also, resting afferent renal nerves activity is elevated in CHF rats, which may highlight a crucial neural mechanism arising from the kidney in the maintenance of enhanced sympathetic drive in CHF.