The role of nitric oxide in the reduction of protein kinase C-induced contractile response in aortae from rats with portal hypertension

Background/Aims: Protein kinase C plays a role in the regulation of vascula r cell contraction but its activity may be reduced by nitric oxide. In port al hypertension, the exact mechanism by which nitric oxide induces vascular hyporeactivity to vasoconstrictors is unclear, The aim of this study was t o investigate the role of the interaction of nitric oxide and protein kinas e C in the vascular reactivity in isolated aortae from portal vein-stenosed rats. Methods/Results: The contractile response to phorbol 12,13-dibutyrate, a pr otein kinase C activator, was significantly reduced in portal vein-stenosed aortae compared to sham-operated aortae. Preincubation with N-nitro-L-argi nine or endothelium removal enhanced the response to phorbol 12,13-dibutyra te, The hyporesponsiveness to phorbol 12,13-dibutyrate in portal vein-steno sed rat aortae was only corrected after endothelium removal, The time cours e of contractions induced by phorbol 12,13-dibutyrate showed that the contr action was maintained for 2 h in sham-operated aortae and decreased to base line in portal vein-stenosed rat aortae, This decrease was inhibited by N-n itro-L-arginine preincubation or endothelium removal, Protein kinase C down regulation caused a more marked reduction of phenylephrine-induced contract ion in portal vein-stenosed aortae than in sham-operated aortae. The time c ourse of total nitric oxide synthase activity in the presence of phorbol 12 ,13-dibutyrate showed a decrease in nitric oxide synthase activity after 30 min in both groups, Nitric oxide synthase activity remained stable for 120 min in sham-operated aortae but returned to basal level in portal vein-ste nosed aortae. Conclusions: Hyporeactivity to vasoconstrictors in portal vein-stenosed rat aortae may be due, in part, to a decrease in protein kinase C activation c aused by nitric oxide overproduction.