Studies on the effect of different inhibitors of arachidonic acid metabolism on glyceryltrinitrate-induced relaxation and cGMP elevation in bovine vascular tissue.

This study was performed in order to investigate the possible involvement of arachidonic acid metabolites in the mediation of glyceryltrinitrate (GTN)-induced relaxation in isolated bovine mesenteric artery (BMA) and vein (BMV) and in bovine coronary artery (BCA). Concentration-effect curves for GTN were established on the different types of vessels, precontracted with 2.5 microM phenylephrine (BMA) or K+-depolarization (BMV and BCA), in the presence or absence of different inhibitors of the arachidonic acid metabolism. The used inhibitors of arachidonic acid metabolism were: 10 microM quinacrine (a phospholipase A2 inhibitor), 100 microM acetylsalicylic acid, 20 microM indomethacin (cyclooxygenase inhibitors), 3 mM tranylcypromine (inhibitor of PGI2 synthesis), 50 microM nordihydroguairetic acid and 40 microM BW 755C (lipoxygenase inhibitors). In addition, SKF 525A (10 microM) was tested on BMA; this agent is considered to block the cytochrome P450-dependent monooxygenase pathway. The effect on the endogenous levels of cyclic nucleotides after treatment with some of the inhibitors were also measured. Quinacrine and acetylsalicylic acid had no statistical significant effect (P greater than 0.05) on the pD2-value for GTN-induced relaxation in BMA, BMV and BCA. The results obtained with indomethacin were very variable. This drug was almost completely without effect on the GTN induced relaxation in BCA. In BMA a significant potentiation of the relaxant response was obtained (P = 0.002), while in BMV a significant inhibition was seen (P = 0.049).(ABSTRACT TRUNCATED AT 250 WORDS)