AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 85-L91, Copyright © 1995 by American Physiological Society
Airways of a hyperresponsive rat strain show decreased relaxant responses to sodium nitroprusside
Y. Jia, L. Xu, S. Heisler and J. G. Martin
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
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.
