Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery.
The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N(G)-nitro-L-arginine (L-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ETB receptor antagonist, 2,6-Dimethylpiperidinecarbonyl-gamma-Methyl-Leu-Nin-(Methoxycarbonyl)-D-Trp-D-Nle (BQ-788), enhanced endothelin-1-induced contraction in control rabbits and decreased the potency of endothelin-1 in diabetic rabbits. Sodium nitroprusside-induced relaxation of basilar arteries was lower in diabetic than in control rabbits. These results suggest that mechanisms underlying rabbit basilar artery hyperreactivity to endothelin-1 include decreased endothelial modulation of endothelin-1-induced contraction, with impaired endothelial endothelin ETB receptor activity; decreased sensitivity to nitric oxide (NO) in vascular smooth muscle; and enhanced participation of muscular endothelin ETA and ETB receptors.
Departamento de Fisiología, Facultad de Farmacia, Universitat de València, Avda Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain. Jose.A.Alabadi@uv.es
José A
JA
Alabadí
Francisco J
FJ
Miranda
Silvia
S
Lloréns
José M
JM
Centeno
Vannina G
VG
Marrachelli
Enrique
E
Alborch
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D044022:Receptor, Endothelin A / Q000819:agonists; D044023:Receptor, Endothelin B / Q000819:agonists; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)