. nNOS gene transfer to RVLM improves baroreflex function in rats with chronic heart failure. Am J Physiol Heart Circ Physiol 285: H1660-H1667, 2003; 10.1152/ajpheart.00239.2003.-We hypothesized that gene transfer of neuronal nitric oxide synthase (nNOS) into the rostral ventrolateral medulla (RVLM) improves baroreflex function in rats with chronic heart failure (CHF). Six to eight weeks after coronary artery ligation, rats showed hemodynamic signs of CHF. A recombinant adenovirus, either Ad.nNOS or Ad.-Gal, was transfected into the RVLM. nNOS expression in the RVLM was confirmed by Western blot analysis, NADPH-diaphorase, and immunohistochemical staining. We studied baroreflex control of the heart rate (HR) and renal sympathetic nerve activity (RSNA) in the anesthetized state 3 days after gene transfer by intravenous injections of phenylephrine and nitroprusside. Baroreflex sensitivity was depressed for HR and RSNA regulation in CHF rats (2.0 Ϯ 0.3 vs. 0.8 Ϯ 0.2 beats ⅐ min Ϫ1 ⅐ mmHg Ϫ1 , P Ͻ 0.01 and 3.8 Ϯ 0.3 vs. 1.2 Ϯ 0.1% max/mmHg, P Ͻ 0.01, respectively). Ad.nNOS transfer into RVLM significantly increased the HR and RSNA ranges (152 Ϯ 19 vs. 94 Ϯ 12 beats/min, P Ͻ 0.05 and 130 Ϯ 16 vs. 106 Ϯ 5% max/mmHg, P Ͻ 0.05) compared with the Ad.-Gal in CHF rats. Ad.nNOS also improved the baroreflex gain for the control of HR and RSNA (1.8 Ϯ 0.2 vs. 0.8 Ϯ 0.2 beats ⅐ min Ϫ1 ⅐ mmHg Ϫ1 , P Ͻ 0.01 and 2.6 Ϯ 0.2 vs. 1.2 Ϯ 0.1% max/mmHg, P Ͻ 0.01). In sham-operated rats, we found that Ad.nNOS transfer enhanced the HR range compared with Ad.-Gal gene transfer (188 Ϯ 15 vs. 127 Ϯ 14 beats/min, P Ͻ 0.05) but did not alter any other parameter. This study represents the first demonstration of altered baroreflex function following increases in central nNOS in the CHF state. We conclude that delivery of Ad.nNOS into the RVLM improves baroreflex function in rats with CHF. sympathetic nerve activity; heart rate; nitric oxide; adenovirus IT HAS BEEN WELL ESTABLISHED that arterial baroreflex function is impaired in patients (8) and animals (48) with chronic heart failure (CHF) and that it is associated with sympathoexcitation (3, 10, 11). This sympathoexcitation, if sustained, clearly aggravates the progression of the CHF state (6). It has been shown that the neuronal isoform of nitric oxide (NO) synthase (nNOS) message and activity are substantially reduced at various central sites in animals with experimental CHF (33). The rostral ventrolateral medulla (RVLM) is the final site of sympathetic processing in the brain and transmits sympathetic excitatory projections to the spinal cord (41). It plays a critical role in the control of arterial pressure, heart rate (HR), and sympathetic outflow from the central nervous system (CNS) (7). As a neuromodulatory substance, NO is believed to elicit effects on several central pathways, including the regulation of sympathetic tone (13). By using immunohistochemistry and NADPH-diaphorase staining, some studies have already demonstrated that nNOS is present in several regions that make up the ...