Since the regulation of vascular function involves complex mutual interactions between NO synthase (NOS) and cyclooxygenase (COX) products, we examined the contribution of NO and prostanoids derived from the COX pathway in modulating aortic baroreceptor resetting during an acute (30 min) increase in arterial pressure in anesthetized rats. Increase in pressure was induced either by administration of the non-selective NOS inhibitor N^g-nitro-L-arginine-methyl ester (L-NAME) or aortic coarctation (COA) with or without treatment with the COX inhibitor indomethacin (INDO) or the selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM). The activity of the aortic depressor nerve and arterial pressure were simultaneously recorded, and the degree of resetting was determined by the shift of the pressure-nerve activity curve using the ratio [systolic pressure at 50% of maximum baroreceptor activity/ systolic pressure] x 100. The magnitude of pressure rise was similar in the different groups (59±6, 53±5, 53±5, 45±5, 49±3 and 41±3 mmHg for COA, L-NAME, INDO+COA, INDO+L-NAME, TRIM+COA and TRIM+INDO+COA, respectively, P=0.27). The degree of resetting that occurred with L-NAME or COA combined with treatment with TRIM was attenuated as compared to COA alone (7±4, 5±2 and 31±6%, respectively, P=0.04). Indomethacin failed to influence baroreceptor resetting to higher pressure but prevented L-NAME and TRIM induced effects (20±7, 21±8 and 32±6% INDO+COA, INDO+L-NAME and INDO+TRIM+COA, respectively,(P=0.38). Baroreceptor gain was affected only by L-NAME. These findings indicate that NO, probably from neuronal origin, may exert stimulatory influence on the degree of rapid baroreceptor resetting to hypertension that involves COX-derived prostanoids.