Effect of axotomy on nitric oxide-dependent cyclic GMP production of rat superior cervical sympathetic ganglia in response to norepinephrine.

Cyclic GMP (cGMP) production in superior cervical sympathetic ganglia (SCG) isolated from rats was markedly enhanced (approx. 4.5-fold) by the addition of L-arginine (L-Arg, 100 microM) plus an inhibitor (3-isobutyl-1-methylxanthine) for cGMP hydrolytic enzyme during in vitro aerobic incubation at 37 degrees C for 10 min. This accelerated accumulation of ganglionic cGMP was effectively reversed by approximately 50% when NG-monomethyl-L-arginine (L-NMMA, 50 microM), a compound that inhibits nitric oxide (NO) synthesis from L-Arg, was further added to the medium. These observations imply that cGMP production with possible involvement of a mechanism depending on NO synthesis may be functionally operating in the ganglionic tissue. Application of norepinephrine (NE, 50 microM) with pargyline, a monoamine oxidase inhibitor, to the medium also elevated the ganglionic cGMP level at a magnitude comparable to that shown by L-Arg addition, while co-addition of L-NMMA largely (approx. -60%) eliminated the NE-induced increase in ganglionic cGMP formation. In axotomized SCG one week prior to examination, where sympathetic neurons were degenerated and reactive proliferation of glial cells was in progress, augmented stimulatory effect (more than 8-fold) of NE on cGMP production was seen compared to that caused in unoperated ganglia or in SCG 1 week following denervation, where preganglionic cholinergic nerve terminals were destroyed. When axotomized SCG were transferred to in vitro incubation conditions, addition of an alpha-1 adrenergic antagonist, prazosin (1 microM) to the medium virtually reduced the accelerative effect of NE to less than 25% of the NE-induced cGMP level in the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)