Esculetin attenuates alterations in Ang II and acetylcholine mediated vascular reactivity associated with hyperinsulinemia and hyperglycemia.

Abstract

Esculetin (6, 7- dihydroxycoumarin) was found to be protective against hepatic and renal damage associated with Streptozotocin (STZ) induced type 1 diabetes, because of its radical scavenging property. However, there are no reports regarding its effect on vascular dysfunction under hyperinsulinemic and hyperglycemic conditions. Hence, the present study aimed to investigate the effect of esculetin on vascular dysfunction under these conditions. Non-genetic model of hyperinsulinemia and hyperglycemia were developed by high fat diet (HFD) feeding and HFD + Streptozotocin (STZ, 35 mg/kg, I.P) treatment in Wistar rats, respectively. Esculetin was administered at 50 and 100 mg/kg/day (P.O, 2 weeks) doses and biochemical, vascular reactivity and immunohistochemical experiments were performed to assess the effect of esculetin on vascular dysfunctions. Esculetin treatment significantly attenuates metabolic perturbations, alleviates insulin levels in hyperinsulinemic condition. Thoracic aorta of hyperinsulinemic and hyperglycemic rats showed hyper-responsiveness to Ang II mediated contraction and impaired acetylcholine mediated relaxation, and esculetin attenuates alterations in vascular reactivity to Ang II and acetylcholine challenges. In addition, immunohistochemical evaluations revealed that esculetin prevents increase in AT1R, AT2R, Keap1, TGF-β, and decrease in ACE2 expression in aorta of hyperinsulinemic and hyperglycemic rats.

• Authors: Almesh Kadakol, Vajir Malek, Santosh Kumar Goru, Anuradha Pandey, Shreyas Bagal, Anil Bhanudas Gaikwad
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 461 Issue 2 Pg. 342-7 (May 29 2015) ISSN: 1090-2104 [Electronic] United States
• PMID: 25887801 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Transforming Growth Factor beta
• Umbelliferones
• Angiotensin II
• Peptidyl-Dipeptidase A
• Ace2 protein, rat
• Angiotensin-Converting Enzyme 2
• Acetylcholine
• esculetin

Topics

• Acetylcholine (metabolism)
• Angiotensin II (metabolism)
• Angiotensin-Converting Enzyme 2
• Animals
• Antioxidants (therapeutic use)
• Aorta (metabolism, pathology)
• Blood Pressure (drug effects)
• Diabetes Mellitus, Experimental (complications, metabolism, pathology)
• Hyperglycemia (complications, metabolism, pathology)
• Hyperinsulinism (complications, metabolism, pathology)
• Hypertension (etiology, metabolism, pathology, prevention & control)
• Male
• Peptidyl-Dipeptidase A (analysis)
• Rats, Wistar
• Transforming Growth Factor beta (analysis)
• Umbelliferones (therapeutic use)