Simon, Oswald R.; Davis-Mohammed, Patrice
Author Affiliation, Ana.
Department of Basic Medical Sciences
Sustained-stretching tension on guinea pig tracheal muscle produced cGMP-mediated attenuation of contractile tension
Pharmacology Reviews and Communications
Date of Publication
Modulators of guanylate cyclase / cGMP activity were used to demonstrate the presence and the activating stimulus for this enzyme system in the guinea pig tracheal muscle. The results with sodium nitroprusside (0.13 mmole), 8-bromo-cGMP (0.3 mmole), zaprinast (0.4 mmole), cystamine (0.5 mmole) and methylene blue (0.1 mmole) suggest that cGMP attenuated resting tension in tracheal muscle strips under a 1g stretching tension. Under similar experimental conditions, zaprinast (0.4 mmole) and cystamine (0.5 mmole) produced results indicative of cGMP-mediated attenuation of histamine-induced (0.02-0.4 mmole) contractile tension in tracheal muscle strips, but the magnitude of the modulators effects were reduced as contractile tension increased; this finding ruled out contractile tension as the activating stimulus for the enzyme. However, when the muscle strips were subjected to various magnitudes of sustained-stretching tensions (0.5g to 4g), contractions produced by single doses of histamine (0.04 mmole and 0.2 mmole) were increasingly potentiated by cystamine (0.5 mmole) and increasingly inhibited by zaprinast (0.4 mmole). The magnitude of inhibition with zaprinast was dependent on the magnitude of sustained-stretching tension placed on the muscle. Also, histamine-induced contractions in the absence and presence of cystamine suggest that sustained-stretch on the muscle elicited the length/tension relationship, but the contractile tension was attenuated by cGMP. In comparison, rapidly-applied stretch on the muscle produced stress-relaxation which was not affected by the modulators of cGMP activity. Therefore, the observed effects suggest that sustained-stretch on the tracheal muscle activated guanylate cyclase leading to cGMP-mediated attentuation of histamine-induced contractions.....