Mechanism of endothelial nitric oxide-dependent vasorelaxation induced by wine polyphenols in rat thoracic aorta

The mechanisms by which red wine polyphenolic compounds (RWPCs) induced end othelium-dependent relaxation were investigated in rat thoracic aorta rings with endothelium. RWPCs produced relaxation that was prevented by the nitr ic oxide (NO) synthase inhibitor, N-omega-nitro-L-arginine-methyl-ester. Th is relaxation was abolished in the absence of extracellular calcium in the medium or in the presence of the Ca2+ entry blocker, La3+, but it was not a ffected by the nonselective K+ channels blocker, tetrabutylammonium. N-Ethy l-maleimide (NEM), a sulfhydryl alkylating agent, abolished vasorelaxation produced by RWPCs and acetylcholine but not that produced either by the sar coendoplasmic reticulum Ca2+-adenosine triphosphatase (ATPase) pump inhibit or, cyclopyazonic acid (CPA) or the calcium ionophore, ionomycin. Neither p ertussis toxin (PTX) nor cholera toxin (CTX) inhibited the vasorelaxant eff ect of RWPC. The effect of RWPC was not affected by the phospholipase C (PL C) blocker, L-alpha-glycerophospho-D-myo-inositol 4-monophosphate (Gro-Dip) , and the phospholipase Az pathway blockers, quinacrine and ONO-RS-082. Fin ally the protein kinase C (PKC) inhibitor, GF 109203X, and tyrosine kinase inhibitors, tyrphostin A-23 and genistein, did not impair the response to R WPCs. These results suggest that RWPCs produce endothelium-NO-derived vasor elaxation through an extracellular Ca2+-dependent mechanism via an NEM-sens itive pathway. They also show that PTX- or CTX-sensitive G proteins, activa tion of PLC or PLA(2) pathways, PKC, or tyrosine kinase may not be involved .