Potentiation of endothelium-dependent vasorelaxation of mesenteric arteries from spontaneously hypertensive rats by gemigliptin, a dipeptidyl peptidase-4 inhibitor class of anti-diabetic drug.
10.4196/kjpp.2018.22.6.713
- Author:
Hae Jin KIM
1
;
Eun Bok BAEK
;
Sung Joon KIM
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. sjoonkim@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Dipeptidyl peptidase-4;
Endothelium dependent relaxation;
Gemigliptin;
Hypertension;
Hyperglycemia
- MeSH:
Animals;
Endothelium;
Glucagon-Like Peptide 1;
Glucagon-Like Peptide-1 Receptor;
Hyperglycemia;
Hypertension;
Incretins;
Mesenteric Arteries*;
NG-Nitroarginine Methyl Ester;
Nitroprusside;
Plasma;
Pyrogallol;
Rats;
Rats, Inbred SHR*;
Relaxation;
Sitagliptin Phosphate;
Superoxides;
Vasodilation*
- From:The Korean Journal of Physiology and Pharmacology
2018;22(6):713-719
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 µM gemigliptin while not by saxagliptin and sitagliptin up to 10 µM. The ACh-EDR of SHR MA was also improved by 1 µM gemigliptin while similar recovery was observed with higher concentration (10 µM) 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 µM 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.
