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Characterization of $ET_B$ Receptor-mediated Relaxation in Precontracted Mesenteric Artery from Streptozotocin-induced Diabetic Rats  

Eom, Yang-Ki (Department of Pharmacology, College of Medicine, Pusan National University)
Kim, Koan-Hoi (Department of Pharmacology, College of Medicine, Pusan National University)
Rhim, Byung-Yong (Department of Pharmacology, College of Medicine, Pusan National University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.9, no.5, 2005 , pp. 305-314 More about this Journal
Abstract
Diabetes mellitus is associated with vascular complications, including an impairment of vascular function and alterations in the reactivity of blood vessels to vasoactive substances in various vasculature. In the present study, the authors have observed endothelin-B ($ET_B$) receptor agonist-induced relaxation in precontracted mesenteric arterial segments from streptozotocin (STZ)-induced diabetic rats, which was not shown from control rats or in other arterial segments from diabetic rats. Accordingly, the goal of this study was to investigate in what way STZ-induced diabetes altered reactivity of the mesenteric arterial bed and to examine the causal relaxation, if any, between this $ET_B$ receptor-mediated relaxation and endothelial paracrine function, especially nitric oxide (NO) production. The relaxation induced by $ET_B$ agonists was not observed in mesenteric arteries without endothelium. The relaxation to $ET_B$ agonists was completely abolished by pretreatment with BQ788, but not by BQ610. $N_{\omega}-nitro-L-arginine$ methyl ester and soluble guanylate cyclase inhibitors, methylene blue or LY83583 significantly attenuated the relaxant responses to $ET_B$ agonists, respectively. When the expression of eNOS and iNOS was evaluated on agarose gel stained with ethidium bromide, the expression of eNOS mRNA in diabetic rats was significantly decreased, but the expression of iNOS was increased compared with control rats. Furthermore, the iNOS-like immunostaining was densely detected in the endothelium and slightly in the arterial smooth muscle of diabetic rats, but not in control rats. These observations suggest that $ET_B$ receptor may not play a role in maintaining mesenteric vascular tone in normal situation. However, the alterations in $ET_B$ receptor sensitivity were found in diabetic rats and lead to the $ET_B$ agonist-induced vasorelaxation, which is closely related to NO production. In the state of increased vascular resistance of diabetic mesenteric vascular bed, enhanced NO production by activation of iNOS could lead to compensatory vasorelaxation to modulate adequate perfusion pressure to splanchnic area.
Keywords
$ET_B$ receptors; Mesenteric artery; Relaxation; Streptozotocin; Diabetes; Nitric oxide;
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