BIPHASIC EFFECT OF SNP ON OPOSSUM ESOPHAGEAL LONGITUDINAL MUSCLE - INVOLVEMENT OF CGMP AND EICOSANOIDS

Effects of nitric oxide (NO)-containing compounds on opossum esophageal longitudinal smooth muscle in vitro were examined. Sodium nitroprusside (SNP) and authentic NO produced a biphasic concentration-dependent relaxation-contraction sequence in the esophageal longitudinal muscle (ELM) but only a concentration-dependent relaxation of the lower esophageal sphincter (LES) and no effect in the esophageal circular muscle. A cell membrane-permeable analogue of guanosine 3',5'-cyclic monophosphate (cGMP), 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) also produced relaxation-contraction sequence in the ELM and relaxation of the LES. The guanylate cyclase inhibitors methylene blue (MB) and LY-83583 increased resting tone and had no significant effect on SNP-induced relaxation of ELM. However, they abolished the SNP-and NO-induced contraction of ELM. The cyclooxygenase inhibitor indomethacin had no effect on ELM relaxation and abolished the contractions due to SNP, NO, and 8-BrcGMP. These studies show that in the ELM 1) SNP, authentic NO, and 8-BrcGMP cause a biphasic relaxation-contraction sequence; 2) MB and LY-83583 blocked contraction but not the relaxation associated with SNP and NO; and 3) indomethacin blocked contractions but not the relaxation due to SNP, NO, and 8-BrcGMP. These results suggest that in the ELM, NO donors exert an inhibitory action that is largely cGMP independent and an excitatory action via a cGMP-dependent pathway involving endogenous eicosanoids of the cyclooxygenase pathway.