Effects of Paricalcitol and Enalapril on Atherosclerotic Injury in Mouse Aortas

Abstract

Aims: This study investigated the protective effect of vitamin D analog paricalcitol combined with angiotensin-converting enzyme inhibitor (enalapril) on aortic oxidative injury in atherosclerotic mice. Methods: Female mice were treated for 16 weeks as follows: (1) ApoE deficient + vehicle, (2) ApoE deficient + paricalcitol (200 ng 3 times a week), (3) ApoE deficient + enalapril (30 mg/l in drinking water), (4) ApoE deficient + paricalcitol + enalapril, and (5) wild-type controls. Results: ApoE-deficient mice developed hypertension which was prevented by enalapril or enalapril + paricalcitol treatment but not by paricalcitol treatment. Histology showed atherosclerotic plaque in the aorta of ApoE-deficient mice which was prevented by paricalcitol, enalapril, and paricalcitol + enalapril treatments. Aortic malondialdehyde levels, NADPH oxidase subunit p22^phox, manganese-superoxide dismutase (Mn-SOD), inducible nitric oxide synthase, monocyte chemoattaractant protein-1, tumor necrosis factor (TNF)-α, and cyclooxygenase-2 protein expressions increased, whereas glutathione levels, CuZn-SOD, and endothelial protein expressions decreased in ApoE-deficient mice compared to controls. Treatment with paricalcitol and enalapril alone or in combination protected the inflammatory and oxidative endothelial injury of the aorta in atherosclerotic mice. Conclusion: Combination therapy affords greater protection against aortic inflammatory and oxidative injury in atherosclerosis than monotherapy.

Effect of combining an ACE inhibitor and a VDR activator on glomerulosclerosis, proteinuria, and renal oxidative stress in uremic rats

“…Treatment with enalapril also prevented the increase as did cotherapy with the two drugs. Recent studies from members of our group also showed amelioration by paricalcitol and enalapril of uremiainduced NADPH oxidase activity in rat cardiac tissue (20) and of apolipoprotein E knockout-induced NADPH oxidase activity in the mouse aorta (21). Since active vitamin D compounds have been shown to negatively regulate the RAAS (26,56), the inhibition of p22 phox by either enalapril or paricalcitol points to a role for the RAAS in the oxidative stress seen in the kidney in the current study.…”

Antioxidant and renoprotective effects of paricalcitol on experimental contrast-induced nephropathy model

“…We speculate that paricalcitol decreases contrast-induced explosion of serum MDA and renal TBARS levels, therefore ameliorating the renal histopathological findings (tubular necrosis, proteinaceous casts and medullary congestion) in the paricalcitol plus CIN group. Of note, paricalcitol has been shown to improve cardiac oxidative injury in uremic and aortic oxidative injury in atherosclerotic rats [9,23]. Paricalcitol has been shown to attenuate ciclosporin Ainduced nephropathy by suppression of inflammatory and apoptotic factors through inhibition of some protein kinase-signalling pathways [5].…”

Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model

“…It has also been recently reported that the combination of paricalcitol and enalapril treatment ameliorates oxidative injury by suppressing reactive oxygen species generating enzyme NADPH oxidase activity and by up regulating the antioxidant defense system in a uremic rat model of atherosclerosis. 11 It is not known, however, whether paricalcitol can protect against oxidative stress in amikacin-induced nephrotoxicity.…”