We and other laboratories have reported that arterial baroreflex-mediated control of heart rate is blunted in spontaneously hypertensive rats (SHR) compared with normotensive controls. Recently, we reported that atrial natriuretic peptide (ANP) microinjected into the caudal nucleus tractus solitarii of SHR further blunts this defect. The present study tested the hypothesis that ANP modulates arterial baroreflex-mediated control of sympathetic nervous system activity. Nine-week-old, male SHR (n=29) and normotensive Wistar-Kyoto control rats (n=24) were instrumented for microinjection into the caudal nucleus tractus solitarii and for direct measurement of arterial blood pressure, heart rate, and lumbar sympathetic nervous system activity. After urethane- and α-chloralose-induced anesthesia, arterial baroreflex-mediated control of heart rate and lumbar sympathetic nerve activity was assessed during phenylphrine- (5 to 40 μg · kg-1 · min-1) induced increases and sodium nitroprusside- (15 to 300 μg · kg-1 · min-1) induced decreases in mean blood pressure before and after micronjection of ANP (50 ng) or monoclonal antibody to ANP (0.55 μg) into the caudal nucleus tractus solitarii. ANP reduced and the antibody enhanced the sensitivity of baroreflex-mediated control of both heart rate and lumbar sympathetic nerve activity in SHR but not in Wistar-Kyoto controls (P<.05). Arterial baroreflex sensitivity was unchanged with control microinjections of vehicle or mouse IgG in SHR. These data suggest that endogenous ANP in the caudal nucleus tractus solitarii may contribute to the development and/or maintenance or hypertension in SHR by blunting baroreflex-mediated control of sympathetic nervous system activity.