Background: Prolonged incubation of porcine isolated coronary artery (PCA) to lipopolysaccharide (LPS) causes a moderate reduction in vessel constrictive responsiveness. This has been attributed mainly to the induction of nitric oxide synthase (NOS). We aimed to investigate the role of induction of cyclo-oxygenase (COX) and expression of endothelin receptor 1-A (ET1(A)) in modulating the vascular responses of PCA in vitro.
Methods: Segments of PCA were exposed to 100 microg ml(-1) LPS overnight. L-Arginine 0.4 mM was included in the medium in some preparations to examine the influence of intracellular nitric oxide, and the influence of extracellular donor sodium nitroprusside (SNP) was also examined in separate experiments. After overnight incubation, the contractile function of the artery was evaluated by the isometric tension recording test. The non-selective NOS inhibitor (L-NAME), non-selective COX inhibitor (indomethacin), COX-1 inhibitor (FR 122047), COX-2 inhibitor (NS 398), and ET1(A) receptor antagonist (FR 139317) were added into the organ bath 30 min before eliciting contractile responses to KCl or U46619 separately or in combinations. Vascular relaxations to 10 nM Substance P (SP) were also assessed.
Results: L-Arginine did not potentiate the effects of LPS. SNP caused a quantitatively larger reduction in the responsiveness to KCl and U46619 compared with 100 microg ml(-1) LPS. Post exposure to a combination of indomethacin and FR 139317, indomethacin or NS 398 alone enhanced the inhibitory effects of LPS, but FR 122047 or FR 139317 alone failed to modify the responses to LPS. L-NAME fully reversed the changes induced by LPS combined with indomethacin and NS398. In terms of the relaxation by SP, LPS failed to change the magnitude; none of the agents used affected the response except L-NAME which abolished it.
Conclusion: NOS and COX-2 are both activated by overnight exposure to LPS in vascular smooth muscle from PCA in vitro. The prostanoid produced by COX-2 functionally antagonizes the effects of induction of NOS.