抄録
The developmental changes in acetylcholine (ACh)-induced vasodilator response in isolated rabbit spinal arterioles were investigated with special reference to endogenous nitric oxide (NO) and vasodilator prostaglandins. Spinal arterioles from juvenile (1–3 months) and adult (12–14 months) Japanese white rabbits were dissected, cannulated, and perfused. In both age groups, ACh produced a comparable vasodilation of the arterioles preconstricted with KCl (20–40 mM). In juveniles, a major part of the ACh-induced vasodilation was eliminated by the cyclo-oxygenase inhibitor indomethacin (10 μM), whereas the effect of the NO synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 30 μM) was smaller. In contrast, L-NAME completely eliminated the ACh-induced vasodilation in the adult group, which was partially restored with additional treatment with L-arginine (1 mM). Vasodilations induced by isocarbacyclin (a prostacyclin analogue) and cilostazol (a cAMP-phosphodiesterase inhibitor) was attenuated in the adult, whereas that induced by sodium nitroprusside was unaltered. These results suggest that the mechanisms of ACh-induced vasodilation of rabbit spinal arterioles change with the development: prostanoid-associated in juveniles and NO-associated in the adult. Such age-related modulation of the mediator roles of prostanoids and NO might represent an increase in NO production and a decreased sensitivity of the vascular smooth muscle to cAMP-mediated responses with age.
