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This study examined the influence of overnight storage on endothelium-independent contractions to 5-hydroxytryptamine (5-HT), endothelium-dependent contractions to NG-nitro-L-arginine methyl ester (L-NAME), and endothelium-dependent relaxations to substance P (SP) and L-arginine, using the porcine isolated splenic artery. In endothelium-intact (E+) segments from fresh porcine isolated splenic arteries or segments from the same vessels stored overnight at 4 degrees C, either in Krebs-Henseleit saline or in Krebs-Henseleit saline containing 1 mM L-arginine, 5-HT caused concentration-related contractions that were similar under all three conditions. Overnight storage enhanced contractions of the splenic artery to L-NAME, an effect not observed if the vessels were co-stored with 1 mM L-arginine. L-NAME failed to contract endothelium-denuded (E-) segments from fresh tissues or tissues stored overnight, indicating that its constrictor effects were endothelium-dependent. SP caused concentration-related, endothelium-dependent relaxations of the splenic artery that were inhibited by 100 microM L-NAME, indicating that the relaxations could be attributed to the stimulated release of NO from endothelial cells. Established contractions to 100 microM L-NAME in E+ segments from fresh tissues, or segments from the same tissues stored overnight at 4 degrees C, either in Krebs-Henseleit saline or in Krebs-Henseleit saline containing 1 mM L-arginine, were all reversed by 1 mM L-arginine to similar extents, indicating that overnight storage did not affect endothelium-dependent dilator responses to L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

The nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), produced large endothelium-dependent contractions in isolated segments of the porcine splenic artery, equivalent to approximately 30% of the maximum responses to 5-hydroxytryptamine (5-HT). These responses were inhibited by 1mM L-arginine, but not by either 1mM D-arginine or the superoxide anion scavenger, superoxide dismutase. However, L-NAME-induced contractions were markedly inhibited by the cyclooxygenase inhibitor, flurbiprofen, and the lipoxygenase inhibitor, 2,3,5-tri-methyl-6-(12-hydroxy-5,10-dodecadiynyl)1,4-benzoquinone (AA-861). The combined cyclooxygenase and lipoxygenase inhibitor 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW-755C) abolished L-NAME-induced contractions. These findings suggest that suppression of endothelial nitric oxide synthase in the porcine isolated splenic artery results in activation of arachidonic metabolism and production of vasoconstrictor eicosanoids.