Altered content and modulation of soluble guanylate cyclase in the cerebellum of rats with portacaval anastomosis

It is shown that the glutamate-NO-cGMP pathway is impaired in cerebellum of rats with portacaval anastomosis in vivo as assessed by in vivo brain micr odialysis in freely moving rats. NMDA-induced increase in extracellular cGM P in the cerebellum was significantly reduced (by 27%) in rats with portaca val anastomosis. Activation of soluble guanylate cyclase by the NO-generati ng agent S-nitroso-N-acetyl-penicillamine and by the NO-independent activat or YC-1 was also significantly reduced (by 35-40%), indicating that portaca val anastomosis leads to remarkable alterations in the modulation of guanyl ate cyclase in cerebellum. Moreover, the content of soluble guanylate cycla se was increased ca. two-fold in the cerebellum of rats with portacaval ana stomosis. Activation of soluble guanylate cyclase by NO was higher in lymph ocytes isolated from rats with portacaval anastomosis (3.3-fold) than in ly mphocytes from control rats (2.1-fold), The results reported show that the content and modulation of soluble guanyl ate cyclase are altered in brain of rats with hepatic failure, resulting in altered function of the glutamate-NO-cGMP pathway in the rat in vivo. This may lead to alterations in cerebral processes such as intercellular commun ication. circadian rhythms, including the steep-waking cycle, long-term pot entiation, and some forms of learning and memory. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.