Influence of hypertension on nitric oxide synthase expression and vasculareffects of lipopolysaccharide in rat mesenteric arteries

1 Experiments were designed to investigate the effects of the inducible nit ric oxide synthase (iNOS) stimulator, lipopolysaccharide (LPS), on noradren aline (NA) responses and on NOS activity and its expression in intact mesen teric resistance arteries (MRAs) from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2 In MRAs from WKY, LPS (10 mu g ml(-1); 1-5 h) reduced the vasoconstrictor responses to NA (0.1-30 mu M) in the presence, but not in the absence of L -arginine (L-Arg, 10 mu M). However, in SHR arteries, LPS induced an incuba tion-time dependent reduction of NA responses in the absence, as well as th e presence, of L-Arg. The LPS inhibitory effect was reduced by the non-spec ific NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME, 100 mu M) and t he selective iNOS inhibitor, aminoguanidine (100 mu M). 3 L-NAME alone similarly shifted the concentration-response curve to NA lef tward in arteries from both strains, while aminoguanidine had no effect. L- Arg shifted the curve to NA rightward only in SHR MRAs. 4 Basal activity of both iNOS and constitutive NOS (conversion of [H-3]-L-A rg to [H-3]I-L-citrulline) was similar in arteries from both strains. After 5h incubation with LPS, only iNOS activity in arteries from SHR was increa sed. 5 Basal iNOS protein expression was undetectable; basal endothelial (eNOS) protein expression was similar in arteries from both strains, while neurona l (nNOS) was greater in arteries from SHR. LPS induced iNOS protein express ion, that was higher in arteries from SHR than in those from WKY. 6 These results indicate that NO production, via iNOS induction, is greater than in those from MRAs from SHR to WKY.