The role of nitric oxide and protein kinase C in lipopolysaccharidemediated vascular hyporeactivity.
OBJECTIVE
Overactivation of nitric oxide and protein kinase C (PKC) pathway has been reported to play a role in the pathogenesis of vascular hyporesponsiveness of endotoxic shock. In this study we investigated the role of nitric oxide and PKC in lipopolysaccharide (LPS) mediated vascular hyporeactivity.


METHODS
Contraction to phenylephrine and endothelium-dependent and independent vasodilation in the presence and absence of a nonspecific NO inhibitor (L-NAME) and potent PKC inhibitor (chelerythrine) were examined.


RESULTS
In LPS treated rats, contractile response of aortic rings to phenylephrine and relaxation in response to acetylcholine were reduced, but relaxation induced by sodium nitroprusside remained unchanged. The attenuation of contractile response to phenylephrine in the presence of L-NAME and chelerythrine was more pronounced in aortic ring isolated from LPS treated rats than control. L-NAME decreased acetylcholine -dependent vasodilation in both group but it was more pronounced in LPS treated rats. Chelerythrine pretreatment improved maximal relaxation to acetylcholine in aortic ring isolated from LPS treated rats.


CONCLUSIONS
These data indicate that the vascular hyporesponsiveness to phenylephrine and acetylcholine after treatment with LPS may be related to an enhanced NO production in the smooth muscle cells and PKC plays a role as an intracellular mediator of LPS-induce NOS activity and vascular suppression.
Karimi
Gholamreza
G
Department of Pharmacodynamy and Toxicology, Pharmacy School, Mashhad, Iran. gho_karimi@yahoo.com
Fatehi
Zahra
Z
Gholamnejad
Zahra
Z
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D008070:Lipopolysaccharides; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester