Combination Therapy with Paricalcitol and Enalapril Ameliorates Cardiac Oxidative Injury in Uremic Rats

Vol. 29, No. 5, 2009

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Original Report: Laboratory Investigation

Combination Therapy with Paricalcitol and Enalapril Ameliorates Cardiac Oxidative Injury in Uremic Rats
Kazim Husain^a, Leon Ferder^a, Masahide Mizobuchi^b, Jane Finch^b, Eduardo Slatopolsky^b

^aDepartment of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, P.R., and
^bRenal Division, Washington University School of Medicine, St. Louis, Mo., USA

Address of Corresponding Author

Am J Nephrol 2009;29:465-472 (DOI: 10.1159/000178251)

Key Words

Paricalcitol
Enalapril
Cardiac oxidative stress
Uremia

Abstract

Aims: This study investigated the protective effect of the angiotensin-converting enzyme inhibitor, enalapril, and the vitamin D analog, paricalcitol, alone or in combination, on cardiac oxidative stress in uremic rats. Methods: Rats were made uremic by 5/6 nephrectomy and treated for 4 months as follows: (1) uremic + vehicle (n = 11); (2) uremic + enalapril (30 mg/l in drinking water, n = 13); (3) uremic + paricalcitol (200 ng 3× week, n = 6); (4) uremic + enalapril + paricalcitol (n = 14), and (5) controls (n = 6). Results: Cardiac NADPH oxidase activity increased by 300% in uremic rats compared to normal controls. Treatment with enalapril, paricalcitol or the combination of the two protected uremic rats from cardiac oxidative stress by inhibiting enzyme activity. Cardiac malondialdehyde (MDA) levels were significantly increased in uremic rats compared to normal controls. Only the combination therapy inhibited the increase in MDA levels in uremic rats. Cardiac glutathione was significantly reduced in uremic rats compared to normal controls. Enalapril, paricalcitol or the two in combination all protected against this reduction in glutathione. Cardiac copper/zinc superoxide dismutase (CuZn-SOD) activity decreased whereas manganese (Mn-SOD) activity increased in uremic rats compared to controls. Both mono and combination therapies ameliorated the alterations in cardiac SOD activity seen in uremic rats. Conclusion: Enalapril, paricalcitol and their combined therapy afford protection against cardiac oxidative stress in uremia.

Author Contacts

Prof. Kazim Husain, PhD
Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine
PO Box 7004, Ponce, PR 00732-7004 (USA)
Tel. +1 787 840 2575, ext. 2153, Fax +1 787 841 3736
E-Mail kazimhusain@hotmail.com

Article Information

Received: July 20, 2008
Accepted: October 20, 2008
Published online: November 26, 2008
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 1, Number of References : 46

Medline Abstract (ID 19033720)

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