Blockade of nitric oxide-evoked smooth muscle contractions by an inhibitor of guanylyl cyclase

NITRIC oxide-induced contractile responses of smooth muscle were studied in vitro in guinea-pig small intestine. Application of nitric oxide (NO; 0.3- 30 μM) evoked a small initial relaxation followed by a marked contractile response in plexus-containing longitudinal smooth muscle preparations from small intestine. The extent of the NO-evoked contractile response was dose- dependent and the response was blocked by tetrodotoxin. Atropine significantly reduced the NO-evoked contraction and the remaining part was abolished by the NK₁-receptor antagonist CP 96,345. An inhibitor of soluble guanylyl cyclase, ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one), abolished the NO-evoked contractile response. The results suggest that NO, in addition to the classical direct smooth muscle relaxing effect, causes activation of excitatory neurones, via a pathway utilizing soluble guanylyl cyclase, which leads to a smooth muscle contraction.