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Interaction between irbesartan, peroxisome proliferator-activated receptor (PPAR-γ), and adiponectin in the regulation of blood pressure and renal function in spontaneously hypertensive rats

Journal of Physiology and Biochemistry volume 72, pages 593–604 (2016)Cite this article

Abstract

Adiponectin exerts vasodilatory effects. Irbesartan, an angiotensin receptor blocker, possesses partial peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist activity and increases circulating adiponectin. This study explored the effect of irbesartan alone and in combination with adiponectin on blood pressure, renal hemodynamic excretory function, and vasoactive responses to angiotensin II and adrenergic agonists in spontaneously hypertensive rat (SHR). Irbesartan was given orally (30 mg/kg/day) for 28 days and adiponectin intraperitoneally (2.5 μg/kg/day) for last 7 days. Groups of SHR received either irbesartan or adiponectin or in combination. A group of Wistar Kyoto rats (WKY) served as controls. Metabolic data and plasma samples were taken on days 0, 21, and 28. In acute studies, the renal vasoconstrictor actions of angiotensin II (ANGII), noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) were determined. SHR control rats had a higher mean blood pressure than the WKY (132 ± 7 vs. 98 ± 2 mmHg), lower plasma and urinary adiponectin, creatinine clearance, urine flow rate and sodium excretion, and oxidative stress markers compared to WKY (all P < 0.05) which were progressively normalized by the individual drug treatments and to a greater extent by combined treatment. Responses to intrarenal administration of NA, PE, ME, and ANGII were larger in SHR (P < 0.05) than WKY by 20–25 %. Irbesartan enhanced (P < 0.05) responses to NA and PE, while adiponectin blunted responses to all vasoconstrictors (all P < 0.05). Combined treatment in SHR further decreased the renal vascular responses to ANGII. These findings suggest that an interactive relationship may exist between PPAR-γ, alpha adrenoceptors, and ANGII in the renal vasculature of the SHR.

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Acknowledgments

The authors fully acknowledge the Universiti Sains Malaysia, Research grant no. 1001/PFARMASI/815078, provided by Universiti Sains Malaysia for this work.

Sheryar Afzal is a recipient of USM Fellowship from the Institute of Post-Graduate Studies (IPS), Universiti Sains Malaysia (USM), Penang, Malaysia, and this support is gratefully acknowledged.

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Affiliations

  1. Cardiovascular and Renal Physiology Lab, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia

    S. Afzal, M. A. Sattar, Safia Akhtar & Fayyaz Hashmi

  2. Department of Physiology, University College Cork, Cork, Ireland

    Edward J. Johns & Mohammed H. Abdulla

  3. Department of Pharmacology, Universiti Malaya, Kuala Lumpur, 50603, Malaysia

    Nor Azizan Abdullah

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  1. S. Afzal
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  2. M. A. Sattar
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  3. Edward J. Johns
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  4. Mohammed H. Abdulla
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  5. Safia Akhtar
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  6. Fayyaz Hashmi
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  7. Nor Azizan Abdullah
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Correspondence to S. Afzal.

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The present experiment was conducted in Cardiovascular and Renal Physiology Lab, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, 11800, Malaysia

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Afzal, S., Sattar, M.A., Johns, E.J. et al. Interaction between irbesartan, peroxisome proliferator-activated receptor (PPAR-γ), and adiponectin in the regulation of blood pressure and renal function in spontaneously hypertensive rats. J Physiol Biochem 72, 593–604 (2016). https://doi.org/10.1007/s13105-016-0497-1

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  • DOI: https://doi.org/10.1007/s13105-016-0497-1

Keywords

  • Angiotensin II
  • Adiponectin
  • Peroxisome proliferator-activated receptor
  • Renal hemodynamics
  • Spontaneously hypertensive rat (SHR)