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 t o strain-related differences in airway responsiveness in the rat. Isol ated tracheal rings from hyperresponsive Fisher rats were confirmed to be more responsive; to carbachol [mean effective concentration (EC(50 )) = 2.45 x 10(-7) M] than those from Lewis (EC(50) = 3.60 x 10(-7) M, P < 0.03) and ACI (EC(50) = 3.85 x 10(-7) M, P < 0.01) rats. Sodium n itroprusside (SNP), a NO donor, caused relaxation of the carbachol (10 (-6) M) contracted tracheal rings, but the half-maximal inhibition con centration (IC50) SNP in Fisher rats (5.60 x 10(-6) M) was significant ly higher than that 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 pr onounced for Fisher than Lewis rats. SNP induced an accumulation of gu anosine 3',5'-cyclic monophosphate (cGMP) in cultured tracheal smooth muscle cells (TSM). Fisher TSM produced less cGMP on exposure to SNP c ompared with TSM from ACI (P < 0.01) and Lewis (P < 0.0001) rats. A de creased guanylyl cyclase activity may account for the impaired relaxan t effect of SNP in Fisher rats.