BASAL OR STIMULATED RELEASE - EVIDENCE OF EDRF (NO) RELEASE BY TP-RECEPTOR AGONIST U46619

Many vasoconstrictor substances have been demonstrated as being vasodi lators through the mechanism of endothelium-derived relaxing factor (E DRF)-nitric oxide (NO) release. The authors have hypothesized that all naturally secreted vasoconstrictor substances may potentially be vaso dilators as well in order to maintain an adequate physiological vascul ar tone and have suggested a new term (vasoactivator) for vasoconstric tors. They have recently found that the vasoconstriction induced by a mimetic (U46619) of thromboxane A(2) (TXA(2)), a naturally secreted va soconstrictor substance released from platelets, may be markedly influ enced by the presence of endothelium in the porcine coronary artery (P CA). This may be due to basal (spontaneous) release of EDRF (NO) or st imulated biosynthesis/release by thromboxane A(2). The present study w as designed to further investigate whether stimulated release of EDRF (NO) by TXA(2) exists. PCA rings were mounted in organ baths under a p hysiologic pressure. The concentration-contraction curves to U46619 we re compared in endothelium-intact (+E, n=7) and endothelium-denuded (- E, n=4) rings. At the maximal contraction induced by U46619 (-6.5 log M), N-G-nitro-L-arginine (L-NNA, -4 log M) was added. In separate expe riments, at resting condition, L-NNA (-4 log M) or U46619 (-7.7 log M) was added and the force changes were recorded. After twenty minutes, U46619 (-7.7 log M) or L-NNA (-4 log M) was added to study the force d eveloped. U46619-induced contraction forces were significantly higher in the -E rings at the concentrations of -9.5 to -7.5 log M and L-NNA induced further contractions in the +E (P < 0.01) but not in the -E ri ngs. In resting conditions, L-NNA induced 0.12 g and further addition of U46619 (-7.7 log M) induced 8.8 g contraction force (P < 0.0001). O n the other hand, U46619 (-7.7 log M) induced only 0.88 g contraction force whereas further addition of L-NNA induced a large force (7.43 g, P < 0.0001). The authors conclude that although basal release exists in the PCA this cannot explain the large difference between the +E art eries and the -E or L-NNA-incubated arteries, and therefore, TXA(2) st imulates EDRF (NO) biosynthesis/release in the porcine coronary artery .