Airways of a hyperresponsive rat strain show decreased relaxant responses to sodium nitroprusside.
The aim of the current studies was to investigate the possibility that a decreased relaxant response to nitric oxide (NO) might contribute to strain-related differences in airway responsiveness in the rat. Isolated tracheal rings from hyperresponsive. Fisher rats were confirmed to be more responsive to carbachol [mean effective concentration (EC50) = 2.45 x 10(-7) M] than those from Lewis (EC50 = 3.60 x 10(-7) M, P < 0.03) and ACI (EC50 = 3.85 x 10(-7) M, P < 0.01) rats. Sodium nitroprusside (SNP), a NO donor, caused relaxation of the carbachol (10(-6) M) contracted tracheal rings, but the half-maximal inhibition concentration (IC50) SNP in Fisher rats (5.60 x 10(-6) M) was significantly higher than in Lewis (1.34 x 10(-6) M, P < 0.001) and ACI rats (1.13 x 10(-6) M, P < 0.0005). The inhibitory effect of SNP on airway responsiveness to inhaled methacholine (MCh) in vivo was also less pronounced for Fisher than Lewis rats. SNP induced an accumulation of guanosine 3',5'-cyclic monophosphate (cGMP) in cultured tracheal smooth muscle cells (TSM). Fisher TSM produced less cGMP on exposure to SNP compared with TSM from ACI (P < 0.01) and Lewis (P < 0.0001) rats. A decreased guanylyl cyclase activity may account for the impaired relaxant effect of SNP in Fisher rats.
Jia
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Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Xu
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Heisler
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Martin
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D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D009712:Nucleotides, Cyclic / Q000096:biosynthesis; D051381:Rats; D011912:Rats, Inbred ACI; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D009573:Nitrites; D009712:Nucleotides, Cyclic; D016210:Methacholine Chloride; D009599:Nitroprusside; D002217:Carbachol; D006152:Cyclic GMP