Current Hypertension Reviews - Volume 5, Issue 1, 2009

Uric acid is an intermediate product formed from the metabolism of purine. The high serum uric acid level is termed as hyperuricemia. Gout, a metabolic disorder is associated with high uric acid level in the body. Hyperuricemia has been noted to upregulate the expression of inflammatory mediators and adhesion molecules. Hyperuricemia has been suggested to be an independent risk factor involved in the pathogenesis of vascular endothelial dysfunction. Moreover, hyperuricemia has been demonstrated to play a pivotal role in the pathogenesis of various cardiovascular disorders such as atherosclerosis, hypertension, coronary artery disease and heart failure. The present review critically discussed the possible detrimental role of hyperuricemia in cardiac and vascular endothelial function. Moreover, the signaling mechanism involved in the pathogenesis of hyperuricemia-induced cardiovascular dysfunction has been discussed. In addition, the pharmacological interventions to ameliorate hyperuricemia-induced cardiovascular dysfunction have been delineated.

The physiologic sequelae of Renal Artery Stenosis (RAS) results from narrowing of renal artery lumen which leads to diminished renal perfusion. The consequences of RAS range from asymptomatic to refractory hypertension to ischemic nephropathy eventually leading to end-stage renal disease (ESRD).

The regulation of blood pressure is dependent on multiple interacting mechanisms that influence body fluid volume, sodium balance, and vascular function. Impairments in kidney function can lead to activation of the reninangiotensin system and inappropriate sodium and fluid retention leading to hypertension. The heme-heme oxygenase system is a recently identified antihypertensive regulatory mechanism. Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, free iron and carbon monoxide (CO). Biliverdin is converted to bilirubin by biliverdin reductase and is an endogenous antioxidant. In this review, we discuss the role of HO in regulating kidney function and blood pressure in normal conditions and during hypertension. CO modulates renal vascular tone and salt transport. CO exerts renal vasodilatory effects causing an increase in renal blood flow. Induction of HO also alters expression and activity of renal heme enzymes that regulate renal hemodynamics and renal function. While HO inhibition causes an increase in blood pressure, renal HO induction attenuates the development of hypertension in several models of hypertension suggesting an important role for HO in regulation of renal function and blood pressure.

An increase in arterial blood pressure (BP) is common following the onset of stroke. Although there is evidence suggesting that this acute elevation of BP is associated with a poor clinical outcome in both ischemic and hemorrhagic stroke patients, optimal treatment strategies are currently unknown. The management of BP in the first 24 hours following stroke lends itself to two competing rationales in both stroke sub-types. In ischemic stroke patients, BP reduction may improve outcome, potentially by reducing hemorrhagic transformation and edema formation. Conversely, antihypertensive therapy may also reduce cerebral blood flow (CBF) in the penumbra, exacerbating ischemic injury. Similarly, BP reduction may improve outcome in hemorrhagic stroke patients by preventing the expansion of the hematoma and reducing perihematoma edema. The perihematoma region has also been hypothesized to have ischemic penumbral properties, although the evidence for this is limited. Nonetheless, there is the potential for detrimental CBF compromise following BP reduction in hemorrhagic stroke as well. Recently, advanced neuro-imaging techniques have made it possible to test many of the hypotheses related to the etiology of BP elevation and optimal treatment strategies in acute stroke. This article summarizes concepts and evidence for different BP management strategies in both types of stroke.

High blood pressure levels are associated with increases in circulating levels of inflammation markers which can reflect vascular inflammatory processes, suggesting that hypertension is a low-grade inflammatory process. The vascular inflammation associated with hypertension could be the link between high blood pressure levels and the atherosclerotic process, which is the principal origin of cardiovascular disease, the leading cause of worldwide mortality. High blood pressure levels are accompanied by increases in oxidative stress due to both higher reactive oxygen specie (ROS) production and reduced ROS scavenging by antioxidant defence. This situation favours endothelial function alterations which allow the expression of adhesion molecules and initiation of fatty streak, the earliest structural change in the atherosclerotic process. At the same time, this inflammation, allows endothelial dysfunction since some inflammatory mediators can negatively affect endothelial cell function. Inflammation, therefore, plays a critical role in development and in complications of the atherothrombotic process. Changes in mechanical stress and activation of humoral factors such as the reninangiotensin- aldosterone system can be underlying not only increases in oxidative stress (and consequently endothelial dysfunction) but also the development of the inflammatory process associated with hypertension.

Dendritic cells (DCs) are a key component of the immune system which are capable of sampling antigen and present them to immune effector cells. By modulating the degree and quality of response of these effector cells, DCs represent a decisive element at the earliest phases of any given immune reaction. Recently, the presence of a vascular associated DC system has been described within the vascular wall, more precisely, in the intima and adventitia. These DCs exert important (patho-) physiological functions. For instance, DCs are functional at early stages of atherosclerosis and they contribute to atheroprogression and plaque destabilization. Furthermore, DCs are involved in other inflammatory vascular diseases such as giant cell arteriitis and idiopathic pulmonary hypertension. This review describes recent advances in the physiology and pathophysiology of dendritic cells associated with the vascular wall.

Hypertension is estimated to affect 1 billion people worldwide, and is associated with an increased risk of cardiovascular disease and all-cause mortality. The management of high blood pressure focuses on lifestyle modifications (i.e. diet, exercise, smoking cessation) and drug therapies. Despite these strategies, many patients are still unable to maintain or control their blood pressure within desired levels. Recent research has identified isometric handgrip (IHG) training as a potential therapeutic modality. Results demonstrate a hypotensive effect of IHG training in medicated and unmedicated patients. This novel therapy may be efficacious based on low associated costs and time requirements (33 min/week). The mechanisms coupled with the attenuations in resting blood pressure remain contentious. However, recent evidence has begun to suggest that beneficial modulation of the autonomic nervous system is responsible for the positive changes in blood pressure. While further IHG research is required, the prospect of a novel non-pharmacological therapy for hypertension has major public health implications. This review will summarize the previous literature, discuss future research directions, and describe clinical significance.

Hypertension is a well-recognized complication of excess glucocorticoids, both naturally-occurring and synthetic. Dexamethasone is a potent synthetic glucocorticoid, which has widespread clinical applications. As dexamethasone has purely glucocorticoid activity with negligible mineralocorticoid effects, dexamethasone-induced hypertension (DEXHT) models have been used for studying the mechanisms of glucocorticoid-induced hypertension. This review examines the characteristics and mechanisms of DEX-HT, both in the human and experimental animal models. The roles of hemodynamics, volume, renin-angiotensin-aldosterone system, sympathetic nervous system, vasodilators including nitric oxide, vasoconstrictors and reactive oxygen species in the pathogenesis of DEX-HT are reviewed and differences from hypertension due to naturally occurring steroids discussed.