5-Hydroxytryptamine-induced endothelium-dependent and -independent relaxations in isolated dog anterior spinal small arteries.
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.
Wang
J X
JX
1st Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Ikomi
F
F
Ohhashi
T
T
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D005343:Fibrinolytic Agents; D007211:Indoles; D012702:Serotonin Antagonists; D012701:Serotonin; D008719:Methiothepin; D000077526:Tropisetron; D007650:Ketanserin; C041946:9-O-methanoprostaglandin I; D011464:Epoprostenol; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester