title: 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.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Almesh
authors.initials: A
authors.lastname: Kadakol
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Vajir
authors.initials: V
authors.lastname: Malek
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Santosh Kumar
authors.initials: SK
authors.lastname: Goru
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India.
authors.forename: Shreyas
authors.initials: S
authors.lastname: Bagal
authors.affiliation: Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, India. Electronic address: anil.gaikwad@pilani.bits-pilani.ac.in.
authors.forename: Anil Bhanudas
authors.initials: AB
authors.lastname: Gaikwad
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006946:Hyperinsulinism / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000032:analysis; D014468:Umbelliferones / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D016212:Transforming Growth Factor beta; D014468:Umbelliferones; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D000109:Acetylcholine; C007628:esculetin
keywords: ACE2; Angiotensin II; Esculetin; Hyperglycemia; Hyperinsulinemia; Vascular reactivity