Calcitriol attenuates vascular remodeling in association with alteration of ppET-1/[ET.sub.B]R/eNOS and [ET.sub.A]R expression in acute and chronic phases of kidney ischemia-reperfusion injury in mice

• Published in: Canadian journal of physiology and pharmacology 2023-01, Vol.101 (1), p.8
• Main Authors: Desita, Eryna Ayu Nugra, Arfian, Nur, Setyaningsih, Wiwit Ananda Wahyu, Sari, Dwi Cahyani Ratna
• Format: Article
• Language: English
• Subjects: Analysis; Calcitriol; Care and treatment; Chronic kidney failure; Development and progression; Dosage and administration; Gene expression; Messenger RNA; Nitric oxide; Prevention; Properties; Reperfusion injury; Risk factors
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2022-0130

Kidney ischemia-reperfusion injury (IRI) causes acute kidney injury with increasing risk of maladaptive repair through endothelin-1 (ET-1)/endothelin type A receptor ([ET.sub.A]R) signaling. Calcitriol shows renoprotection in kidney fibrosis, however, its effects on vasoactive substances expression and vascular remodeling following kidney IRI remain unclear. This research aimed to investigate Calcitriol's effects on preproendothelin-1 (ppET-1), [ET.sub.A]R, endothelial nitric oxide synthase (eNOS) mRNA expression and vascular remodeling in acute and chronic phases of kidney IRI in mice. Twenty-five male Swiss mice were randomly divided into five groups (n = 5): SO (sham-operated), IR3 (3 day kidney IRI), IR12 (12 day kidney IRI), IRD3 (3 day kidney IRI + Calcitriol 0.5 pg/kg body weight (BW)/day), and IRD12 (12 day kidney IRI + Calcitriol 0.5 pg/kg BW/day). Ischemiareperfusion injury groups underwent bilateral renal pedicles clamping for 30 min, then reperfusion. Kidneys were harvested for Sirius Red staining to observe interstitial fibrosis and vascular remodeling, polymerase chain reaction to quantify ppET-1, endothelin type B receptor ([ET.sub.B]R), eNOS mRNA expression, and Western blotting to quantify [ET.sub.A]R protein expression. Calcitriol treatment in both phases of kidney IRI showed lower serum creatinine and [ET.sub.A]R protein expression, while higher eNOS and [ET.sub.B]R mRNA expression than IRI-only groups. Furthermore, ppET-1 mRNA expression was higher in IRD3 than IR3, but lower in IRD12 than IR12. Calcitriol also prevented vascular remodeling as indicated by lower wall thickness and higher lumen/wall area ratio than IRI-only groups.