Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension

Vivian Boshra; Amr M. Abbas

doi:10.1515/jbcpp-2016-0145

Article

Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension

Vivian Boshra and Amr M. Abbas

Published/Copyright: March 20, 2017

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 28 Issue 4

Abstract

Background:

Renovascular hypertension (RVH) is a result of renal artery stenosis, which is commonly due to astherosclerosis. In this study, we aimed to clarify the central and peripheral effects of ghrelin on the renin-angiotensin system (RAS) in a rat model of RVH.

Methods:

RVH was induced in rats by partial subdiaphragmatic aortic constriction. Experiment A was designed to assess the central effect of ghrelin via the intracerebroventricular (ICV) injection of ghrelin (5 μg/kg) or losartan (0.01 mg/kg) in RVH rats. Experiment B was designed to assess the peripheral effect of ghrelin via the subcutaneous (SC) injection of ghrelin (150 μg/kg) or losartan (10 mg/kg) for 7 consecutive days. Mean arterial blood pressure (MAP), heart rate, plasma renin activity (PRA), and oxidative stress markers were measured in all rats. In addition, angiotensin II receptor type 1 (AT1R) concentration was measured in the hypothalamus of rats in Experiment B.

Results:

RVH significantly increased brain AT1R, PRA, as well as the brain and plasma oxidative stress. Either SC or ICV ghrelin or losartan caused a significant decrease in MAP with no change in the heart rate. Central ghrelin or losartan caused a significant decrease in brain AT1R with significant alleviation of the brain oxidative stress. Central ghrelin caused a significant decrease in PRA, whereas central losartan caused a significant increase in PRA. SC ghrelin significantly decreased PRA and plasma oxidative stress, whereas SC losartan significantly increased PRA and decreased plasma oxidative stress.

Conclusions:

The hypotensive effect of ghrelin is mediated through the amelioration of oxidative stress, which is induced by RAS centrally and peripherally.

Keywords: angiotensin II receptor type 1 (AT1R); ghrelin; losartan; oxidative stress; plasma renin activity (PRA); renovascular hypertension

Corresponding author: Dr. Amr M. Abbas, Department of Medical Physiology, Faculty of Medicine, Mansoura University, PO Box:35516, Mansoura, Egypt, Phone: +2 01001545048

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-9-19

Accepted: 2017-1-4

Published Online: 2017-3-20

Published in Print: 2017-7-26

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2016-0145

Keywords for this article

angiotensin II receptor type 1 (AT1R); ghrelin; losartan; oxidative stress; plasma renin activity (PRA); renovascular hypertension