Role of glucagon-like peptide- 1 in vascular endothelial dysfunction.
The present study has been undertaken to investigate the effect of exendin-4 (a glucagon-like peptide-1 agonist) in diabetes mellitus (DM) and hyperhomocysteinemia (HHcy)-induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg-1, iv, once) and methionine (1.7% w/w, po, 4 weeks) were administered to rats to produce DM (serum glucose >200 mg d1-1) and HHcy (serum homocysteine >10 microM) respectively. VED was assessed using isolated aortic ring preparation, microscopy of thoracic aorta, and serum nitrite/nitrate concentration. Serum TBARS concentration was estimated to assess oxidative stress. Atorvastatin has been employed as standard agent. Exendin-4 (1 microg kg-1, ip) and atorvastatin (30 mg kg-1, po) treatments significantly attenuated increase in serum glucose and homocysteine but their concentrations remained markedly higher than sham control value. Exendin-4 and atorvastatin treatments markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine-induced endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining, (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum TBARS. However, this ameliorative effect of exendin-4 has been prevented by L-NAME (25 mg kg-1, ip), an inhibitor of NOS. It may be concluded that exendin-4 may activate eNOS due to activation of GLP-1 and consequently reduce oxidative stress to improve vascular endothelial dysfunction.
Goyal
Sandeep
S
Department of Pharmacology, S D College of Pharmacy, Barnala 148 101, India. sangoyal2007@rediffmail.com
Kumar
Suresh
S
Bijjem
Krishnareddy V
KV
Singh
Manjeet
M
D000818:Animals; D000069059:Atorvastatin; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000502:physiology*; D006538:Heptanoic Acids / Q000494:pharmacology; D020138:Hyperhomocysteinemia / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014688:Venoms / Q000494:pharmacology
D006538:Heptanoic Acids; D010455:Peptides; D011758:Pyrroles; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019331:NG-Nitroarginine Methyl Ester