The influence of diabetes on regulatory mechanisms and specific receptors implicated in the contractile response of isolated rabbit carotid arteries to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was greater in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or NG-nitro-L-arginine enhanced contractions in response to endothelin-1 only in control arteries, without modifying the endothelin-1 response in diabetic arteries. Indomethacin, furegrelate (thromboxane A2inhibitor), or cyclo-(D-Asp-Pro-D-Val- Leu-D-Trp) (BQ-123; endothelin ETAreceptor antagonist) inhibited the contractions in response to endothelin-1, the inhibition being greater in diabetic arteries than in control arteries. 2,6-Dimethylpiperidinecarbonyl- γ-methyl-Leu-Nin-(methoxycarbonyl)-D-Trp-D-Nle (BQ-788; endothelin ETBreceptor antagonist) enhanced the contraction elicited by endothelin-1 in control arteries and displaced to the right the contractile curve for endothelin-1 in diabetic arteries. In summary, diabetes induces hyperreactivity of the rabbit carotid artery to endothelin-1 by a mechanism that at least includes: (1) enhanced activity of muscular endothelin ETAreceptors; (2) impairment of endothelin ETBreceptor-mediated nitric oxide (NO) release; and (3) enhancement of the production of thromboxane A2. © 2004 Elsevier B.V. All rights reserved.
Mendeley saves you time finding and organizing research
Choose a citation style from the tabs below