The role of inducible nitric oxide synthase in lipopolysaccharide-mediated hyporeactivity to vasoconstrictors differs among isolated rat arteries.
We investigated whether organ-specific differences exist in the role of inducible nitric oxide synthase (iNOS) in hyporeactivity to vasoconstrictors following 20 h in vitro exposure of isolated superior mesenteric, renal, hepatic and coronary arteries from the rat to bacterial lipopolysaccharide (LPS). LPS attenuated contraction in response to depolarizing KCl in all arteries. Maximum contractile responses to noradrenaline were attenuated in superior mesenteric and hepatic arteries, and those to the thromboxane A(2) analogue U46619 were attenuated in coronary arteries. LPS shifted the concentration-response curve to noradrenaline in renal arteries to the right. Removal of extracellular L-arginine improved the response to noradrenaline in superior mesenteric and renal arteries only. Addition of the iNOS inhibitor aminoguanidine resulted in full recovery of the responses to noradrenaline in superior mesenteric, renal and hepatic arteries. Contractile responses in coronary arteries did not improve after inhibition of iNOS activity. Therefore the pattern of the LPS-induced changes in vascular reactivity, as well as the contribution of iNOS to impaired vascular constriction, differed among vascular beds. These differences are likely to represent a contributory factor in the sepsis-associated redistribution of cardiac output.
Piepot
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HA
Laboratory for Physiology, Institute for Cardiovascular Research Vrije Universiteit (ICaR-VU), Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Groeneveld
A B J
AB
van Lambalgen
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AA
Sipkema
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P
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006499:Hepatic Artery / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects / Q000503:physiopathology; D012772:Shock, Septic / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D009638:Norepinephrine