Role of Nitric Oxide Produced During Endotoxic Shock in Sympathetic Nervous Function

Endotoxin에 의해 생성된 혈관의 nitric oxide가 교감신경계에 미치는 영향

  • 박관하 (군산대학교 해양산업대학 수족병리학과)
  • Published : 1996.12.01

Abstract

Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.

Keywords

References

  1. J. Pharmacol. Exp. Ther. v.190 Peripheral vascular actions of glucocorticoids and their relationship to protection in circulatory shock Altura,B.M.;Altura,B.T.
  2. Eur. J. Pharmacol. v.127 Vascular alpha-adrenoceptor blockade by E. coli endotoxin in the rat Auclair,M.C.;Svinareff,P.;Schmitt,H.
  3. Brain Res. v.573 Potentiation of nicotinic transmission in the rat superior cervical sympathetic ganglion:effect of cGMP and nitric oxide generators Briggs,C.A.
  4. Nitric oxide modulates peripheral sympathetic activity in the myocardium, 2nd Symposium on Endothelium-derived Vasoactive Factor(abstract) Feelisch,M.;Bloch,W.;Reinhardt,M.;Addicks,K.;
  5. Anal. Chem. v.126 Analysis of nitrate, nitrite and [N]nitrate in biological fluids Green,L.C.;Wagner,D.A.;Glogowski,J.;Skipper,P.L.;Winshnok,J.S.;Tannenbaum,S.R.
  6. Eur. J. Pharmacol. v.187 Inhibition o sympathetic neurotransmitter release by modulators of cyclic GMP in canine vascular smooth muscle Greenberg,S.S.;Diecke,F.R.J.;Cantor,E.;Peevy,K.Tanaka,T.P.
  7. J. Physiol v.177 The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rats McGregor,D.D.
  8. Cir. Shock v.17 Plasma catecholamines during endotoxin infusion in conscious unstrained rats:efect of adrenal demedulation and/or guanethidine treatment McKechnie,K.;Dean,H.G.;Furman,B.L.;Parratt,J.R.
  9. Pharmacol. Rev. v.43 Nitric oxide:physiology, pathopysioligy, and pharmacology Moncada,S.;Palmer,R.M.J.;Higgs,E.A.
  10. J. Pharmacol. Exp. Ther. v.255 Frequency-selective compounds and inhibition of cardiovascular reflexes Park,K.H.;Long,J.P.;Cannon,J.G.
  11. Cir. Res. v.71 Nitric oxide is a mediator of hypoxic coronary vasodilatation:relationship to adenosine and cyclooxygenase-derived metabolites Park,K.H.;Rubin,L.E.;Gross,S.S.;Levi,R.
  12. Br. J. Pharmacol. v.53 E. coli endotoxin shock in the cat:treatment with indomethacin Parratt,J.R.;Sturgess,R.M.
  13. Lancet v.338 Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock Petros,A.;Bennett,D.;Vallance,P.
  14. J. Neurochem. v.48 Activation of tyrosine hydroxylase in PC12 cells by the cyclic GMP and cyclic AMP second messenger systems Roskoski,R.Jr.;Roskoski,L.M.
  15. Proc. Soc. Exp. Med. v.65 A pithed rat preparation suitable for assay of pressor substances Shipley,R.E.;Tilden,J.R.
  16. Science v.254 Is nitric oxide the retrograde messenger? Stevens,C.