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Nitric oxide (NO) exerts cytoprotective effects against hepatic ischemia-reperfusion damage. This study was designed to evaluate which isoform of NO synthase (NOS) is implicated in the generation of cytoprotective NO and to investigate whether NO effects are mediated by cyclic GMP (cGMP). After partial ischemia for 45 min, liver damage was estimated by the release into plasma of cytolytic enzymes. Ischemia-reperfusion induced marked increases in plasma creatine kinase and lactate dehydrogenase after 1 h of reperfusion and of aminotransferases after 6 h of reperfusion. The pretreatment of ischemic rats with 8-bromo-cGMP (16 mg/kg i.v. 30 min before ischemia) or with L-arginine (the endogenous precursor of NO, 100 mg/kg i.v.) significantly diminished the ischemia-reperfusion-induced release of all these enzymes. This demonstrates that cGMP possesses hepatoprotective properties. By immunohistochemistry, we observed, after 6 h of reperfusion, an increase in endothelial NOS-III immunoreactivity, particularly in the small arteries and sinusoids. This NOS-III accumulation in endothelial cells could protect the liver against ischemia-reperfusion by the local generation of NO probably via cGMP.

Carbachol and eserine injected into cerebral ventricles of conscious cats evoked aggressive behaviour accompanied with autonomic and motor phenomena. However, db-cGMP also injected into cerebral ventricles of conscious cats elicited autonomic effects with miaowing, restlessness, ear twitching and scratching. When butyrate sodium and butyryc acide were injected intraventricularly no visible gross behavioural phenomena in conscious cats were observed. The gross behavioural effects of db-cGMP were substantially the same when the cats were pretreated by intraventricular injections of aminophylline.

The effects on regeneration of cyclic nucleotides AMP and GMP were studied on small pieces of the planarian worm Dugesia tigrina. db cAMP, 8Br cGMP and substances acting on their metabolism were used in this work (aminophylline, insulin, imidazole). It seems that these second messengers play a role in a mechanism of regulation in which cGMP has a promotive action and cAMP an inhibitive one.