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 response of isolated rabbit carotid arteries to 5-hydroxytryptamine (5-HT) was studied. 5-HT induced a concentration-dependent contraction that was potentiated in arteries from diabetic rabbits with respect to that in arteries from control rabbits. Endothelium removal potentiated 5-HT contractions in arteries from both control and diabetic rabbits but increased the maximum effect 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 in arteries from control rabbits. Aminoguanidine did not modify the 5-HT contraction in arteries from control and diabetic rabbits. Indomethacin inhibited the 5-HT-induced response, and this inhibition was higher in arteries from control rabbits than in arteries from diabetic rabbits. In summary, diabetes enhances the sensitivity of the rabbit carotid artery to 5-HT. In control animals, the endothelium modulated the arterial response to 5-HT by the release of both nitric oxide (NO) and a vasoconstrictor prostanoid. Diabetes enhances endothelial constitutive NO activity and impairs the production of the endothelial vasoconstrictor.
Departamento de Fisiología, Facultad de Farmacia, Universidad de Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain. francisco.j.miranda@uv.es
F J
FJ
Miranda
J A
JA
Alabadí
S
S
Lloréns
R F
RF
Ruiz de Apodaca
J M
JM
Centeno
E
E
Alborch
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007649:Ketamine / Q000009:adverse effects; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006146:Guanidines; D019335:Nitroarginine; D012701:Serotonin; D007649:Ketamine; D019001:Nitric Oxide Synthase; C004479:pimagedine; D007213:Indomethacin