5-Hydroxytryptamine-induced endothelium-dependent and -independent relaxations in isolated dog anterior spinal small...

The mode of action of 5-hydroxytryptamine (5HT) was investigated in isolated dog anterior spinal small arteries. Lower concentrations of 5HT (10(-9)-10(-7) M) caused a dose-dependent contraction and higher concentrations (10(-6)-10(-3) M) produced a dose-dependent relaxation of the arteries precontracted by 10(-7) M U 46619. The 5HT-induced relaxation was significantly antagonized by methiothepin (10(-9)-10(-6) M). Ketanserin (10(-6) M) and ICS 205-930 (3 x 10(-6) M) did not affect the 5HT-induced relaxation of the arteries. The relaxant response to 5HT was reduced significantly by mechanical rubbing of the endothelial cells. The 5HT-induced endothelium-independent relaxation was also antagonized significantly by methiothepin (10(-6) M). Aspirin (5 x 10(-5) M) or N omega-nitro-L-arginine methyl ester (L-NAME) (10(-6) M) significantly suppressed the 5HT-induced endothelium-dependent relaxation. L-Arginine (10(-3) M) also significantly reversed the L-NAME induced reduction of the 5HT-induced endothelium-dependent relaxation. Treatment with L-NAME in the presence of aspirin also produced much greater reduction of the 5HT-induced endothelium-dependent relaxation. Isocarbacyclin (10(-9)-10(-5) M) induced a concentration-dependent relaxation of the isolated spinal small arteries precontracted by 10(-7) M U 46619. These results suggest that 5HT induces endothelium-dependent and -independent relaxations of the isolated anterior spinal small arteries mainly via activation of 5HT1-like receptor and that endogenous nitric oxide and vasodilative prostaglandins may contribute to the 5HT-induced endothelium-dependent relaxation of the arteries.