Diabetes-induced changes in endothelial mechanisms implicated in rabbit carotid arterial response to 5-hydroxytryptamine

The influence of diabetes on endothelial mechanisms implicated in the respo nse of isolated rabbit carotid arteries to 5-hydroxytryptamine (5-HT) was s tudied. 5-HT induced a concentration-dependent contraction that was potenti ated in arteries from diabetic rabbits with respect to that in arteries fro m control rabbits. Endothelium removal potentiated 5-HT contractions in art eries from both control and diabetic rabbits but increased the maximum effe ct only in arteries from diabetic rabbits. Incubation of arterial segments with N-G-nitro-L-arginine (L-NA) enhanced the contractile response to 5-HT. This L-NA enhancement was greater in arteries from diabetic rabbits than i n arteries from control rabbits. Aminoguanidine did not modify the 5-HT con traction in arteries from control and diabetic rabbits. Indomethacin inhibi ted the 5-HT-induced response, and this inhibition was higher in arteries f rom control rabbits than in arteries from diabetic rabbits. In summary, dia betes enhances the sensitivity of the rabbit carotid artery to 5-HT. In con trol animals, the endothelium modulated the arterial response to 5-HT by th e release of both nitric oxide (NO) and a vasoconstrictor prostanoid. Diabe tes enhances endothelial constitutive NO activity and impairs the productio n of the endothelial vasoconstrictor. (C) 2000 Elsevier Science B.V. All ri ghts reserved.