We reported previously that endothelium-intact superior mesenteric arteries (SMA) from N--nitro-L-arginine (L-NNA)-treated hypertensive rats (LHR) contract more to norepinephrine (NE) than SMA from Control rats. Others have shown that nitric oxide synthase (NOS)-inhibition increases cyclo-oxygenase (COX) function and expression. We hypothesized that augmented vascular sensitivity to NE in LHR arteries is caused by decreased NOS dilation and increased COX product constriction. We observed that the EC₅₀ for NE is lower in LHR SMA compared to Control (Control: -6.37 ± .04, LHR: *-7.89 ± .09 log mol/L). Endothelium removal lowered the EC50 (Control: -7.95 ± .11, LHR: *-8.44 ± .13 log mol/L) and increased maximum tension in Control (Control: *1036 ± 38 vs. 893 ± 21 mg) but not LHR SMA (928 ± 30 vs. 1066 ± 31 mg). Thus augmented NE sensitivity in LHR SMA depends largely on decreased endothelial dilation. NOS inhibition (L-NNA, 10^-4 mol/L) increased maximum tension and EC₅₀ in Control arteries but not in LHR arteries. In contrast, COX inhibition decreased maximum tension in Control arteries suggesting COX products augment contraction. Indomethacin did not affect NE contraction in L-NNA-treated or denuded arteries. In Control SMA loaded with the fluorescent NO indicator, DAF-2DA, indomethacin increased and L-NNA decreased NO release. Therefore COX products appear to inhibit NO production to augment NE contraction. With chronic NOS inhibition, this modulating influence is greatly diminished. Thus, in NOS-inhibition hypertension, decreased activity of both COX and NOS pathways profoundly disrupts endothelial modulation of contraction. * significantly different from Control for p < 0.05.