Effect of endothelium on diabetes-induced changes in constrictor responses mediated by 5-hydroxytryptamine in rat aorta

• Published in: Journal of cardiovascular pharmacology Vol. 22; no. 3; p. 423
• Main Authors: Sikorski, B W, James, G M, Glance, S D, Hodgson, W C, King, R G
• Format: Journal Article
• Language: English
• Published: United States 01-09-1993
• Subjects: Amphetamines - pharmacology; Animals; Aorta - drug effects; Arginine - analogs & derivatives; Arginine - pharmacology; Body Weight - drug effects; Diabetes Mellitus, Experimental - physiopathology; Endothelium - physiology; In Vitro Techniques; Ketanserin - pharmacology; Male; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Nitroarginine; Organ Size - drug effects; Papaverine - pharmacology; Potassium - pharmacology; Rats; Rats, Wistar; Serotonin - pharmacology; Serotonin Receptor Agonists - pharmacology; Vasoconstriction - drug effects
• ISSN: 0160-2446
• DOI: 10.1097/00005344-199309000-00012

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.