The role of nitric oxide on contractile impairment during endotoxemia in rat diaphragm muscle.
We examined the contribution of nitric oxide (NO) on the contractile impairment in diaphragm muscles of endotoxemic rats. Force-frequency relationship was depressed 24 h after lipopolysaccharide administration. 7-Nitroindazole, aminoguanidine and 1H-[1,2,4]Oxadiazole (4,3-a)quinoxalin-1-one (ODQ) partially restored the contractile impairment, Nomega-Nitro-L-Arginine (L-NNA) was ineffective. K+ contractions were reduced by 50% in endotoxemic muscles, 7-nitroindazole partially recovered, while aminoguanidine and L-NNA were ineffective. Verapamil reduced contractility to a greater extent in endotoxemic muscles. Caffeine and ryanodine contractions were augmented during endotoxemia without NOS contribution. L-NNA, 7-nitroindazole, ODQ and hemoglobin did not affect, but aminoguanidine completely restored partially inhibited neurotransmission by d-tubocurarine. Endotoxemia did not change membrane potentials and neurotransmitter release but slightly increased excitability. At this stage of endotoxemia, (1) constitutive NOS appears to be the dominant isoform, (2) NO does not have a major role on contractile dysfunction and (3) impairment could be explained by altered sensitivity of the voltage sensor. (4) NO does not substantially modulate neuromuscular transmission in normal and endotoxemic rats.
Sara
Yildirim
Y
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey. ysara@hacettepe.edu.tr
Ertunc
Mert
M
Onur
Rustu
R
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects / Q000503:physiopathology; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D008070:Lipopolysaccharides; D003473:Neuromuscular Nondepolarizing Agents; D010069:Oxadiazoles; D011810:Quinoxalines; D014665:Vasodilator Agents; D012433:Ryanodine; D019335:Nitroarginine; D009569:Nitric Oxide; D002110:Caffeine; D014700:Verapamil; D019001:Nitric Oxide Synthase; C004479:pimagedine; C080122:7-nitroindazole; D014403:Tubocurarine