Abnormal activation of K+ channels underlies relaxation to bacterial lipopolysaccharide in rat aorta.
We have examined the role of K+ channels in mediating vasorelaxation produced by bacterial lipopolysaccharide (LPS) in endothelial-denuded strips of rat aorta precontracted with phenylephrine (1 microM). Salmonella typhosa LPS (0.1 microgram/ml) caused significant relaxation of tension which peaked at approximately 4hr. The K+ channel blocker, tetraethylammonium chloride (TEA; 10 mM), fully reversed these relaxations whether applied before or after long term exposure to LPS. L-arginine, the substrate for nitric oxide synthase, caused large relaxations in tissues incubated with LPS that were markedly inhibited by TEA. In contrast, TEA or L-arginine had little effect on phenylephrine contractions in control tissues. Furthermore, the inducible nitric oxide synthase inhibitor, aminoguanidine (0.4 mM), reversed the effects of LPS and blocked responses to TEA. These results suggest that activation of K+ channels, possibly Ca-activated K+ channels, through induction of the nitric oxide synthase pathway, may well be responsible for endotoxin-mediated hyporeactivity to vasoconstrictor agents in vascular smooth muscle.
Hall
S
S
Rayne Institute, St. Thomas' Hospital, London, United Kingdom.
Turcato
S
S
Clapp
L
L
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012485:Salmonella typhi; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D010656:Phenylephrine; D019789:Tetraethylammonium; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; C004479:pimagedine