Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 25, 2015; 6(10): 1168-1178
Published online Aug 25, 2015. doi: 10.4239/wjd.v6.i10.1168
Simvastatin, atorvastatin, and pravastatin equally improve the hemodynamic status of diabetic rats
María J Crespo, José Quidgley
María J Crespo, Departments of Physiology and Anesthesiology, University of Puerto Rico-School of Medicine, San Juan, PR 00936-5067, United States
María J Crespo, José Quidgley, Departments of Physiology, University of Puerto Rico-School of Medicine, San Juan, PR 00936-5067, United States
Author contributions: Crespo MJ and Quigley J contributed equally to this work.
Supported by MBRS-RISE, No. R25-GM061838; and RCMI, No. G12-RR03051.
Institutional review board statement: Ethics of the study was approved by the Institutional Animal Care and Use Committee of the University of Puerto Rico-Medical Sciences Campus. The protocol number is 2590108.
Institutional animal care and use committee statement: Institutional animal care and use committee: All experiments were approved by the Institutional Animal Care and Use Committee of the University of Puerto Rico-Medical Sciences Campus (Protocol number: 2590108), and adhered to guidelines established by the National Institutes of Health and the American Veterinary Medical Association.
Conflict-of-interest statement: No conflict of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. María J Crespo, Departments of Physiology and Anesthesiology, University of Puerto Rico-School of Medicine, GPO Box 365067, San Juan, PR 00936-5067, United States. maria.crespo3@upr.edu
Telephone: +1-787-7530120 Fax: +1-787-7530120
Received: April 25, 2015
Peer-review started: April 28, 2015
First decision: June 9, 2015
Revised: July 28, 2015
Accepted: August 16, 2015
Article in press: August 17, 2015
Published online: August 25, 2015
Abstract

AIM: To investigate if the effect of statins improving cardiovascular (CV) status of diabetics is drug-specific or class-dependent, and the underlying mechanisms involved.

METHODS: We compared the results of daily administration over a four-week period of a low dose (10 mg/kg per day) of atorvastatin (AV), simvastatin (SV), and pravastatin (PV) on cardiac performance in diabetic rats. Echocardiographic variables were tested, as well as systolic blood pressure (SBP), acetylcholine (ACh)-induced relaxation, plasma cholesterol levels, and perivascular fibrosis. Malondialdehyde (MDA) and 4-hydroxyalkenal (4-HAE), and endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) protein levels were also measured in cardiac and aortic homogenates.

RESULTS: In untreated diabetic rats, cholesterol levels were higher than in control rats (CT; n = 8, P < 0.05), and the low dose of statins used did not modify these levels. In diabetic rats, SBP was higher than in CT, and was significantly reduced by all three statins (n = 10, P < 0.05). Echocardiographic parameters (EF, SV, and COI) were all lower in untreated diabetic rats than in CT (n = 10, P < 0.05). These CV parameters were equally improved by all three statins. The maximal relaxation (EMax) induced by ACh in aortic ring from diabetic rats was also improved. Moreover, this relaxation was abolished by 1 mmol/L NG-nitro-L-arginine methyl ester, suggesting the involvement of a NO-dependent mechanism.

CONCLUSION: AV, SV, and PV are equally effective in improving CV performance in diabetic rats. All tree statins decreased media thickness, perivascular fibrosis, and both MDA and 4-HAE in the aortas of diabetic rats, without affecting eNOS and iNOS protein levels. The observed hemodynamic benefits are cholesterol-independent. These benefits appear to be secondary to the improved endothelial function, and to the reduced vascular tone and remodeling that result from decreased oxidative stress.

Keywords: Statins, Diabetes, Oxidative stress, Cardiac function, Perivascular fibrosis

Core tip: Despite evidence that statins are useful therapeutic tools in treating diabetes, questions remain as to whether their effects are drug-specific or class-dependent, what mechanisms underlie these effects, and which statin is the most appropriate. We found that atorvastatin, simvastatin, and pravastatin are equally effective in improving cardiovascular performance in Type 1 diabetic rats, and that the observed benefits are likely to be secondary to the reduction of oxidative stress by these drugs.