Altered reactivity of gastric fundus smooth muscle in the mouse with targeted disruption of the kinin B1 receptor gene

Relaxing action of sodium nitroprusside (SNP) was significantly reduced in the stomach fundus of mice lacking the kinin B1 receptor (B1−/−). Increased basal cGMP accumulation was correlated with attenuated SNP induced dose-dependent relaxation in B1−/− when compared with wild type (WT) control mice. These responses to SNP were completely blocked by the guanylate cyclase inhibitor ODQ (10 μM). It was also found that Ca2+-dependent, constitutive nitric oxide synthase (cNOS) activity was unchanged but the Ca2+-independent inducible NOS (iNOS) activity was greater in B1−/− mice than in WT animals. Zaprinast (100 μM), a specific phosphodiesterase inhibitor, increased the nitrergic relaxations and the accumulation of the basal as well as the SNP-stimulated cGMP in WT but not in B1−/− stomach fundus. From these findings it is concluded that the inhibited phosphodiesterase activity and high level of cGMP reduced the resting muscle tone, impairing the relaxant responses of the stomach in B1−/− mice. In addition, it can be suggested that functional B2 receptor might be involved in the NO compensatory mechanism associated with the deficiency of kinin B1 receptor in the gastric tissue of the transgenic mice.