Cardiovascular Journal of Africa: Vol 28 No 3 (May/June 2017)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 3, May/June 2017 AFRICA 141
Cardiovascular Topics
Resveratrol did not alter blood pressure in rats with
nitric oxide synthase-inhibited hypertension
Mehmet Aydin, Buket Gungor, A Secil Akdur, Hakki Engin Aksulu, Coskun Sılan, Ibrahim Susam,
Ali Kemal Cabuk, Gizem Cabuk
Abstract
Background: Inhibition of nitric oxide synthase (NOS) is a
well-known experimental model of hypertension (HT). It was
shown that oxidative stress contributes to the pathogenesis of
HT. Resveratrol is a potent anti-oxidant that is found in red
grapes, peanuts and red wine. It improves the NO response
and increases endothelial NOS expression, which causes
endothelium-dependent vasorelaxation as well as renal vaso-
dilation. We aimed to explore the effects of resveratrol on
blood pressure, the water–salt balance and sodium excretion
as a reflection of renal function in NOS-inhibited rat models.
Methods: Thirty-five male Sprague-Dawley rats (200–250
g) were used in this study. In order to obtain hypertension
models, an NOS inhibitor, N-nitro-L-arginin (L-NNA) was
used. The rats were randomly divided into five groups:
controls (given water and 0.8% salty diet) and four groups
[given L-NNA, resveratrol (RSV) eluent, RSV, and L-NNA
+ RSV]. Blood pressures were measured indirectly by the tail-
cuff method on the first, seventh and 10th days. At the end of
the study protocol (10th day), fluid balance, glomerular filtra-
tion rate, fractional sodium excretion, and blood and urine
sodium and creatinine levels were measured.
Results: At the end of the study protocol, blood pressures
were higher in only the L-NNA group (117.8 ± 3.5 vs 149.5
± 2.1 mmHg; p < 0.05), as expected. Additional applications
of RSV with L-NNA could not prevent the increase in blood
pressure (122.8 ± 7.3 vs 155.4 ± 4.4 mmHg; p < 0.05). There
were no remarkable changes in water–salt balance and renal
function with the application of resveratrol.
Conclusion: Resveratrol was unable to prevent or reverse
blood pressure increase in NOS-inhibited rats.
Keywords: hypertension, NOS, resveratrol, anti-oxidant, sodium
excretion
Submitted 30/12/14, accepted 10/7/16
Cardiovasc J Afr 2017; 28: 141–146
DOI: 10.5830/CVJA-2016-069
Essential hypertension (HT) is one of the leading causes
of preventable deaths and a major risk factor for serious
disorders such as coronary heart disease, heart failure, peripheral
vascular disease, renal failure and stroke. Pathogenesis of HT
is multifactorial and synthesis and/or release of nitric oxide
(NO), which regulates local blood flow and modulates sodium
reabsorption, plays a role in this process.
In order to shed light on the multifactorial pathophysiological
mechanisms of hypertension and to improve preventative and
therapeutic strategies, many experimental models have been
used. One of these experimental models is impairment of NO
production in the blood vessel layer, which is a major pathway
for the development of hypertension, by using nitric oxide
synthase (NOS) inhibitors.1,2
Acute or chronic inhibition of NO production by NOS
inhibitors causes hypertension,3-7 and the degree of elevation of
blood pressure is dose and time dependent. With total inhibition
of NOS with high doses, increased periferal resistance comes
to the fore as the underlying cause; however, water and salt
retention, activation of the symphathetic system and oxidative
stress are important contributors. 8-10
Oxidative stress was shown to be related to inadequate
natriuresis and vasodilatation by means of impaired expression
Department of Cardiology, Tepecik Training and Research
Hospital, Izmir, Turkey
Mehmet Aydin, MD
Ibrahim Susam, MD
Ali Kemal Cabuk, MD,
Department of Clinical Trials, Turkish Medicines and
Medical Devices Agency, Turkish Ministry of Health,
Ankara, Turkey
Buket Gungor, MD
Department of Clinical Pharmacology, Canakkale State
Hospital, Turkish Ministry of Health, Canakkale, Turkey
A Secil Akdur, MD
Department of Pharmacology, School of Medicine,
Canakkale Onsekiz Mart University, Terzioglu Campus,
Canakkale, Turkey
Hakki Engin Aksulu, MD
Coskun Silan, MD
Nanoscience and Technology Research and Application
Center (NANORAC), Canakkale Onsekiz Mart University,
Terzioglu Campus, Canakkale, Turkey
Coskun Silan, MD
Department of Cardiology, Buca Seyfi Demirsoy State
Hospital, Izmir, Turkey
Gizem Cabuk, MD