We evaluated the potential participation of endogenous brain neuropeptide Y (NPY) in central cardiovascular regulation, using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p.). Bilateral microinjection of NPY (4.65 pmol) into the caudal one-third level of the nucleus tractus solitarius (NTS), the terminal site for baroreceptor afferent fibers, promoted a significant suppression of the baroreceptor reflex (BRR) response. The maximal inhibition occurred at 30-40 min postinjection, and amounted to -42.7 +/- 8.6% (mean +/- S.E.M., n = 9). The same treatment, however, only caused transient (approximately 5 min) hypotension and bradycardia. Blocking the endogenous NPY activity at the NTS with its antiserum appreciably enhanced the sensitivity of BRR response (+ 59.2 +/- 18.8%, mean +/- S.E.M., n = 6), but had no appreciable effect on systemic arterial pressure or heart rate. These results suggest that neurons that contain NPY may participate in central cardiovascular regulation by tonically suppressing the BRR response, possibly by exerting an influence on the baroreceptive neurons at the NTS.