We have evaluated the interactions of the vasoconstrictors noradrenaline(NA), the thromboxane A2 (TXA2) analog U46619 and ET-1 with the NO/cGMP pathway as well as the mechanisms involved in NO/cGMP-induced relaxation in isolated piglet (2 week old) intrapulmonary arteries as compared to mesenteric and coronary arteries. Arterial rings (2-3 mm in length, 0.5-2 mm in diameter) were mounted for isometric tension recording in Krebs solution. Except for the experiments with acetylcholine (Ach), endothelium was mechanically removed. Cumulative concentration-response curves were carried out for vasodilators in arteries contracted by NA, U46619 or ET-1. cGMP was assayed by an acetylated 125I-cGMP radioimmunoassay kit.
In pulmonary vessels the contractions induced by U46619 (1 mM) and ET-1 (3 nM) (but not those induced by 10 mM NA) were unaffected by endothelium removal(P > 0.05, t test). U46619- and ET-1- contracted arteries showed reduced relaxant responses to Ach, sodium nitroprusside (SNP), atrial natriuretic peptide and 8-bromocyclic-GMP (but not to forskolin) as compared to NA-contracted arteries (P < 0.05). In contrast, SNP fully relaxed mesenteric and coronary arteries precontracted by U46619 and ET-1. SNP (10 mM) increased three fold (P < 0.05) the cGMP content in pulmonary arteries and this increase was not modified by either NA, U46619 or ET-1. The inhibitory action of U46619 (but not that of ET-1) on the relaxant responses to SNP was reversed by the protein kinase C (PKC) inhibitor staurosporine (100 nM).