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Efficacy of the superoxide dismutase mimetic tempol in animal hypertension models

a meta-analysis

Dornas, Waleska C.a; Silva, Maísaa; Tavares, Ricardob; de Lima, Wanderson G.a,c; dos Santos, Rinaldo C.d; Pedrosa, Maria L.a,c; Silva, Marcelo E.a,d

doi: 10.1097/HJH.0000000000000422

Objective: Considering the growing body of evidence that indicates the contribution of superoxide anions (O2) and other reactive oxygen species (ROS) to the development of hypertension, we assessed whether animal models of hypertension have a benefic effect with tempol, a superoxide dismutase mimetic, to help augment the design of future studies.

Methods: Studies published between July 1998 and December 2012 on blood pressure (BP) in different hypertensive models were obtained after an electronic and manual search of PubMed. In-depth analyses of the methodological quality of the studies and the mean arterial pressure (MAP) changes after treatment with tempol were performed, as well as the subgroup analyses on the route of tempol delivery.

Results: Out of the 144 identified studies, 28 were included after screening. The data showed that tempol reduced MAP by computing the standardized mean difference with the value of 4.622 (95% confidence interval 3.24–5.99). The quality of studies included in the meta-analysis was category II; however, omission of details in the trials might have biased the results. There was substantial heterogeneity in the results with an I2 of 94.45%, which persisted after stratifying for the route of tempol delivery.

Conclusion: In conclusion, this analysis shows that antioxidant treatment with tempol can reduce BP, suggesting that ROS plays a role in the pathogenesis of increased BP in the hypertension models used in the current research practice.

aResearch in Biological Sciences – NUPEB, Federal University of Ouro Preto

bDepartment of Statistics, Institute of Exact and Biological Sciences, Federal University of Ouro Preto

cDepartment of Biological Sciences, Institute of Exact and Biological Sciences, Federal University of Ouro Preto

dDepartment of Foods, School of Nutrition, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil

Correspondence to Marcelo E. Silva, PhD, Professor of Experimental Nutrition, Department of Foods, School of Nutrition, Federal University of Ouro Preto, (UFOP) Campus Universitário Morro do Cruzeiro, CEP 35400-000, Ouro Preto, Minas Gerais, Brazil. Tel: +55 31 3559 1805; fax: +55 31 3559 1828; e-mail:

Abbreviations: BP, blood pressure; cGMP, cyclic guanosine monophosphate; CI, confidence interval; DOCA, deoxycorticosterone acetate; DSS, Dahl salt-sensitive; ET-1, endothelin-1; ET-B, endothelin type B receptor; HTG, Prague hereditary hypertriglyceridemic; IRI, ischemia–reperfusion injury; L-NAME, L-nitroarginine methyl ester; MAP, mean arterial pressure; MDA, malondialdehyde; NOS, nitric oxide synthase; O2, superoxide anions; ROS, reactive oxygen species; RSNA, renal sympathetic nerve activity; SHRs, spontaneously hypertensive rats; SMD, standardized mean difference; SOD, superoxide dismutase; T4, thyroxine

Received 9 April, 2014

Revised 15 September, 2014

Accepted 16 September, 2014

© 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins