Calcitriol attenuates vascular remodeling in association with alteration of ppET-1/ETBR/eNOS and ETAR expression in acute and chronic phases of kidney ischemia–reperfusion injury in mice

Kidney ischemia–reperfusion injury (IRI) causes acute kidney injury with increasing risk of maladaptive repair through
endothelin-1 (ET-1)/endothelin type A receptor (ETAR) 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), ETAR, 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 μg/kg body weight (BW)/day), and IRD12 (12 day kidney IRI + Calcitriol 0.5 μg/kg BW/day). Ischemia–
reperfusion 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 (ETBR), eNOS mRNA expression, andWestern blotting to quantify ETAR protein expression. Calcitriol
treatment in both phases of kidney IRI showed lower serum creatinine and ETAR protein expression, while higher eNOS and
ETBR 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.