Abstract
Hypertension affects over 25% of the global population and is associated with grave and often fatal complications that affect many organ systems. Although great advancements have been made in the clinical assessment and treatment of hypertension, the cause of hypertension in over 90% of these patients is unknown, which hampers the development of targeted and more effective treatment. The etiology of hypertension involves multiple pathological processes and organ systems, however one unifying feature of all of these contributing factors is oxidative stress. Once the body's natural anti-oxidant defense mechanisms are overwhelmed, reactive oxygen species (ROS) begin to accumulate in the tissues. ROS play important roles in normal regulation of many physiological processes, however in excess they are detrimental and cause widespread cell and tissue damage as well as derangements in many physiological processes. Thus, control of oxidative stress has become an attractive target for pharmacotherapy to prevent and manage hypertension. Resveratrol (trans-3,5,4′-Trihydroxystilbene) is a naturally occurring polyphenol which has anti-oxidant effects in vivo. Many studies have shown anti-hypertensive effects of resveratrol in different pre-clinical models of hypertension, via a multitude of mechanisms that include its function as an anti-oxidant. However, results have been mixed and in some cases resveratrol has no effect on blood pressure. This may be due to the heavy emphasis on peripheral vasodilator effects of resveratrol and virtually no investigation of its potential renal effects. This is particularly troubling in the arena of hypertension, where it is well known and accepted that the kidney plays an essential role in the long term regulation of arterial pressure and a vital role in the initiation, development and maintenance of chronic hypertension. It is thus the focus of this review to discuss the potential of resveratrol as an anti-hypertensive treatment via amelioration of oxidative stress within the framework of the fundamental physiological principles of long term regulation of arterial blood pressure.
Highlights
Hypertension is a serious chronic condition that is a leading cause of morbidity and mortality worldwide (Lawes et al, 2008; Wilkins et al, 2010; Chobanian, 2011)
But largely undefined genetic and environmental influences, other factors that are thought to contribute to chronically elevated arterial blood pressure include: (1) cardiac and vascular remodeling, (2) increased cardiac output and total peripheral resistance, (3) diminished production/responsivity to vasodilators, (4) inflammation, (5) immune reaction (Muller et al, 2011), (6) abnormal cell signaling (Belmonte and Blaxall, 2011), (7) elevated sympathetic nervous tone (Zubcevic et al, 2011), (8) arterial baroreceptor adaptation, (9) over activity of renin-angiotensin-aldosterone system (RAAS) (Savoia et al, 2011) and (10) renal dysfunction (Singh et al, 2010)
Amelioration of oxidative stress has been of interest in the prevention and treatment of hypertension and the use of natural anti-oxidant compounds has been intensively studied in recent years
Summary
Hypertension is a serious chronic condition that is a leading cause of morbidity and mortality worldwide (Lawes et al, 2008; Wilkins et al, 2010; Chobanian, 2011). But largely undefined genetic and environmental influences, other factors that are thought to contribute to chronically elevated arterial blood pressure include: (1) cardiac and vascular remodeling, (2) increased cardiac output and total peripheral resistance, (3) diminished production/responsivity to vasodilators, (4) inflammation, (5) immune reaction (Muller et al, 2011), (6) abnormal cell signaling (i.e., vascular, renal) (Belmonte and Blaxall, 2011), (7) elevated sympathetic nervous tone (Zubcevic et al, 2011), (8) arterial baroreceptor adaptation, (9) over activity of renin-angiotensin-aldosterone system (RAAS) (Savoia et al, 2011) and (10) renal dysfunction (Singh et al, 2010) Notwithstanding this vast diversity of hypertensive processes, a common theme amongst them is the increased presence www.frontiersin.org
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