Myocardial effects of VDR activators in renal failure.
Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Traditional causes such as diabetes, smoking, aging and hypertension do not fully explain the high rate of morbidity from cardiovascular disease seen in these patients. The renin-angiotensin-aldosterone system (RAAS) regulates extracellular volume homeostasis, which contributes to blood pressure stability. Overactivity of this system is involved in the pathophysiology of cardio-renal disease. New evidence suggests that vitamin D receptor activators (VDRAs) have a suppressive effect on the RAAS; however, VDRAs also have anti-inflammatory and anti-fibrotic effects. We have demonstrated that paricalcitol, a VDRA, ameliorates left ventricular hypertrophy (LVH) in uremic rats by up-regulating the VDR, decreasing myocardial PCNA and also decreasing myocardial oxidative stress. Thus, paricalcitol can suppress the progression of LVH, myocardial and perivascular fibrosis and myocardial arterial vessel thickness presumably by up-regulating the VDR. Paricalcitol may prove to have a substantial beneficial effect on cardiac disease and its outcome in patients with CKD. Prospective randomized studies in CKD patients are necessary to confirm these results.
Renal Division, Department of Medicine, Washington University St. Louis, MO 63110, USA.
Masahide
M
Mizobuchi
Hironori
H
Nakamura
Masanori
M
Tokumoto
Jane
J
Finch
Jeremiah
J
Morrissey
Helen
H
Liapis
Eduardo
E
Slatopolsky
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D018450:Disease Progression; D004872:Ergocalciferols / Q000494:pharmacology; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism*; D012084:Renin-Angiotensin System; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C084656:paricalcitol