KMID : 0811720180220060713
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Korean Journal of Physiology & Pharmacology 2018 Volume.22 No. 6 p.713 ~ p.719
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Potentiation of endothelium-dependent vasorelaxation of mesenteric arteries from spontaneously hypertensive rats by gemigliptin, a dipeptidyl peptidase-4 inhibitor class of anti-diabetic drug
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Kim Hae-Jin
Baek Eun-Bok Kim Sung-Joon
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Abstract
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Dipeptidyl peptidase4 (DPP4) inhibitors such as gemigliptin are anti-diabetic drugs elevating plasma concentration of incretins such as GLP-1. In addition to the DPP4 inhibition, gemigliptin might directly improve the functions of vessels under pathological conditions. To test this hypothesis, we investigated whether the acetylcholine-induced endothelium dependent relaxation (ACh-EDR) of mesenteric arteries (MA) are altered by gemigliptin pretreatment in Spontaneous Hypertensive Rats (SHR) and in Wistar-Kyoto rats (WKY) under hyperglycemia-like conditions (HG; 2 hr incubation with 50 mM glucose). ACh-EDR of WKY was reduced by the HG condition, which was significantly recovered by 1 ¥ìM gemigliptin while not by saxagliptin and sitagliptin up to 10 ¥ìM. The ACh-EDR of SHR MA was also improved by 1 ¥ìM gemigliptin while similar recovery was observed with higher concentration (10 ¥ìM) of saxagliptin and sitagliptin. The facilitation of ACh-EDR by gemigliptin in SHR was not observed under pretreatment with NOS inhibitor, L-NAME. In the endotheliumdenuded MA of SHR, sodium nitroprusside induced dose-dependent relaxation was not affected by gemigliptin. The ACh-EDR in WKY was decreased by treatment with 30 ¥ìM pyrogallol, a superoxide generator, which was not prevented by gemigliptin. Exendin-4, a GLP-1 analogue, could not enhance the ACh-EDR in SHR MA. The present results of ex vivo study suggest that gemigliptin enhances the NOS-mediated EDR of the HG-treated MA as well as the MA from SHR via GLP-1 receptor independent mechanism.
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KEYWORD
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Dipeptidyl peptidase-4, Endothelium dependent relaxation, Gemigliptin, Hypertension, Hyperglycemia
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