Interactions of nitric oxide synthase inhibitors and dexamethasone with alpha-adrenoceptor-mediated responses in rat aorta.

1. The effects of NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), their D-isomers, and dexamethasone on noradrenaline (NA)-induced contractions and antagonism by alpha-adrenoceptor antagonists, have been investigated in rat isolated thoracic aortic rings with/without endothelium. 2. NA produced concentration-dependent contractions of isolated aortic rings with EC50 values of 2.41 +/- 0.54 (n = 21) and 28.00 +/- 8.50 (n = 25) nM for endothelium-denuded and -intact preparations respectively. Acetylcholine (ACh) relaxed NA-precontracted rings with intact, but not those denuded of endothelium. 3. Treatment with L-NAME (1-30 microM), or L-NMMA (10-500 microM), but not their D-isomers, resulted in an endothelium-dependent enhancement of NA-induced contractions. Pre-treatment, in vitro, with 0.5 microM dexamethasone neither directly potentiated, nor influenced L-NAME-induced potentiation of NA-mediated contractions in endothelium-intact rings; however, dexamethasone pretreatment reduced EC50 values for NA, and also prevented L-NAME-induced potentiation, in denuded rings equilibrated for 5 h under resting tension. 4. In both intact and denuded rings, phentolamine, prazosin and WB 4101 shifted NA concentration-response curves to the right; L-NAME, and also L-NMMA, but not their D-isomers, reversed the blockade as indicated by significant decreases in NA dose-ratios. In denuded rings, reversal by L-NAME or L-NMMA was prevented following pretreatment with dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)