Effects of peripherally and centrally applied ghrelin on the oxidative stress induced by renin angiotensin system in a rat model of renovascular hypertension.
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.
.
Vivian
V
Boshra
.
Amr M
AM
Abbas
D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D054439:Ghrelin / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D054439:Ghrelin; D019808:Losartan
angiotensin II receptor type 1 (AT1R); ghrelin; losartan; oxidative stress; plasma renin activity (PRA); renovascular hypertension