Your browser doesn't support javascript.
loading
Potentiation of endothelium-dependent vasorelaxation of mesenteric arteries from spontaneously hypertensive rats by gemigliptin, a dipeptidyl peptidase-4 inhibitor class of anti-diabetic drug
The Korean Journal of Physiology and Pharmacology ; : 713-719, 2018.
Article in English | WPRIM | ID: wpr-728032
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Plasma / Pyrogallol / Rats, Inbred SHR / Relaxation / Vasodilation / Nitroprusside / Superoxides / NG-Nitroarginine Methyl Ester / Endothelium / Glucagon-Like Peptide 1 Limits: Animals Language: English Journal: The Korean Journal of Physiology and Pharmacology Year: 2018 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Main subject: Plasma / Pyrogallol / Rats, Inbred SHR / Relaxation / Vasodilation / Nitroprusside / Superoxides / NG-Nitroarginine Methyl Ester / Endothelium / Glucagon-Like Peptide 1 Limits: Animals Language: English Journal: The Korean Journal of Physiology and Pharmacology Year: 2018 Type: Article