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Azilsartan Decreases Renal and Cardiovascular Injury in the Spontaneously Hypertensive Obese Rat

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Abstract

Purpose

Angiotensin II type 1 receptor blockers (ARBs) are widely used in treating hypertension. In the present study, we tested the hypothesis that a novel ARB, azilsartan medoxomil (AZL-M) will prevent renal and cardiovascular injury in the spontaneously hypertensive obese rat (SHROB), a model of cardiometabolic syndrome.

Methods

Male SHROB were treated with vehicle or AZL-M orally for 56 days. Vehicle treated normotensive Wistar-Kyoto (WKY) rats served as controls. The effects of AZL-M on kidney injury, vascular endothelial and heart functions, lipid profile, and glucose tolerance were assessed.

Results

AZL-M demonstrated anti-hypertensive effects along with markedly improved vascular endothelial function in SHROB. In these rats, AZL-M demonstrates strong kidney protective effects with lower albuminuria and nephrinuria along with reduced tubular cast formation and glomerular injury. AZL-M treatment also improved left ventricular heart function, attenuated development of left ventricular hypertrophy, and reduced cardiac fibrosis in SHROB.

Conclusion

Overall, these findings demonstrate kidney and heart protective effects of AZL-M in SHROB, and these effects were associated with its ability to lower blood pressure and improve endothelial function.

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Acknowledgments

We thank Katherine A. Walsh and Priyanka Nervatla from Department of Pharmacology & Toxicology, Medical College of Wisconsin for their excellent technical assistance. We also thank Dr Frantisek Papousek from Institute of Physiology, Academy of Science of the Czech Republic for his valuable comments in interpreting echocardiographic data. These studies were supported by a grant from Takeda Pharmaceuticals Inc., USA. Jan Neckář is supported by Czech Science Foundation grant (13-10267S). Md. Abdul Hye Khan is supported by a Postdoctoral Fellowship from the Midwest Affiliate of the American Heart Association.

Disclosure

No conflicts of interest, financial or otherwise, are declared by the author(s).

Author’s contribution

Md. Abdul Hye Khan designed the study, performed experiments, analyzed data and wrote the manuscript. Jan Neckář designed the study, performed experiments, analyzed data and wrote the manuscript. John D. Imig designed the study and wrote the manuscript. Breana Cummens and Geneva M. Wahl performed experiments, analyzed the data. All authors have thoroughly read the manuscript, agreed on the data interpretation, and approved the final draft submitted.

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Authors and Affiliations

  1. Department of Pharmacology & Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Md. Abdul Hye Khan, Jan Neckář, Breana Cummens, Geneva M. Wahl & John D. Imig

  2. Department of Pharmacology & Toxicology and Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank, Road, Milwaukee, WI, 53226, USA

    John D. Imig

  3. Institute of Physiology, Academy of Sciences, Prague, Czech Republic

    Jan Neckář

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  1. Md. Abdul Hye Khan
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Corresponding author

Correspondence to John D. Imig.

Additional information

Md. Abdul Hye Khan and Jan Neckář contributed equally to the work.

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Khan, M.A.H., Neckář, J., Cummens, B. et al. Azilsartan Decreases Renal and Cardiovascular Injury in the Spontaneously Hypertensive Obese Rat. Cardiovasc Drugs Ther 28, 313–322 (2014). https://doi.org/10.1007/s10557-014-6530-0

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