Effect of endothelium on diabetes-induced changes in constrictor responses mediated by 5-hydroxytryptamine in rat aorta.
We investigated constrictor responses to 5-hydroxytryptamine (5-HT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, a 5-HT2/5-HT1C receptor agonist) of aortic rings from 2- and 6-week streptozotocin-diabetic and vehicle control rats. At 10 g resting tension, maximum responses and -log EC50 values to 5-HT were significantly reduced in endothelium-intact and denuded aortas from 2- and 6-week diabetic rats relative to those from control rats (except for -log EC50 of endothelium-intact rings from 6-week diabetic rats). Removal of endothelium from aortas of 2- and 6-week diabetic and control rats caused significant increases both in -log EC50 values and in maximum responses to 5-HT. DOI caused marked contraction of endothelium-denuded aortas from control rats, but not of endothelium-intact aortas from control rats or aortas (either with or without endothelium) from diabetic rats. The nitric oxide (NO) synthase inhibitor N-nitro-L-arginine (NOLA) significantly potentiated constrictor responses to 5-HT in endothelium-intact aortas from control and diabetic rats. NOLA significantly potentiated constrictor responses to DOI in endothelium-intact aortas from control rats, but not in endothelium-intact aortas from diabetic rats. These results suggest that for aortas from 2- and 6-week diabetic rats, the diminished responses to 5-HT and DOI may be a result of reductions in 5-HT2-receptor-mediated responses of smooth muscle. The results also suggest that 5-HT and DOI can stimulate NO release from endothelial cells.
Sikorski
B W
BW
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
James
G M
GM
Glance
S D
SD
Hodgson
W C
WC
King
R G
RG
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004727:Endothelium / Q000502:physiology; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019335:Nitroarginine; D009929:Organ Size / Q000187:drug effects; D010208:Papaverine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D000662:Amphetamines; D017366:Serotonin Receptor Agonists; D019335:Nitroarginine; D012701:Serotonin; D001120:Arginine; D007650:Ketanserin; D010208:Papaverine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D011188:Potassium