Papaverine-induced and endothelium-dependent relaxation in the isolated rat aortic strip

In the present study, we aimed to obtain further evidence in favour of the hypothesis that nitric oxide (NO) is a major mediator of endothelium-depend ent vasorelaxation and to clarify whether NO plays a role in papaverine-ind uced vasorelaxation. The relaxant effects of acetylcholine (Ach), acidified NaNO2 or papaverine were investigated on isolated helical strips of the ra t thoracic aorta precontracted with phenylephrine in an organ bath containi ng Krebs solution aerated with 95% O-2 and 5% CO2. The relaxation was quant ified as % peak reduction of phenylephrine contracture. Saponin abolished t he relaxant effects of Ach completely whereas it had no effect on the respo nses to acidified NaNO2 or papaverine. N-G-nitro-L-arginine (L-NOARG) reduc ed the effects of Ach significantly, but it was ineffective on the relaxati on induced by acidified NaNO2. The inhibitory action of L-NOARG was partly restored by L-arginine, but not by D-arginine. Hemoglobin, hydroxocobalamin and hydroquinone exhibited significant inhibition on the relaxation evoked by Ach and acidified NaNO2. L-NOARG, hydroxocobalamin and hydroquinone cau sed only limited but significant decrease in the relaxation due to papaveri ne. This phenomenon was also observed by increasing phenylephrine concentra tion leading to an enhancement in the contraction. Our findings strongly su pport the view that Ach-induced relaxation of rat aorta strips is mediated by free NO released from the endothelium and the results suggest that NO ma y indirectly contribute to papaverine-induced relaxation.