Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension

Abstract

Hypertension is a complex condition and is the most common cardiovascular risk factor, contributing to widespread morbidity and mortality. Approximately 90% of hypertension cases are classified as essential hypertension, where the precise cause is unknown. Hypertension is associated with inflammation; however, whether inflammation is a cause or effect of hypertension is not well understood. The purpose of this review is to describe evidence from human and animal studies that inflammation leads to the development of hypertension, as well as the evidence for involvement of oxidative stress and endothelial dysfunction--both thought to be key steps in the development of hypertension. Other potential proinflammatory conditions that contribute to hypertension-such as activation of the sympathetic nervous system, aging, and elevated aldosterone--are also discussed. Finally, we consider the potential benefit of anti-inflammatory drugs and statins for antihypertensive therapy. The evidence reviewed suggests that inflammation can lead to the development of hypertension and that oxidative stress and endothelial dysfunction are involved in the inflammatory cascade. Aging and aldosterone may also both be involved in inflammation and hypertension. Hence, in the absence of serious side effects, anti-inflammatory drugs could potentially be used to treat hypertension in the future.

Figure 1

Schematic diagram illustrating the relationship between inflammation and hypertension and the contributing factors involved. Anti-inflammatory drugs and statins may be effective antihypertensive due to their anti-inflammatory properties.

Figure 2

(a) Diagram illustrating endothelium-dependent relaxation during health. (b) Diagram illustrating mechanism by which inflammation and oxidative stress cause endothelial dysfunction. Inflammatory mediators such as CRP and TNF destabilise eNOS mRNA (thus inhibiting eNOS). NO protects endothelium by inhibiting leukocyte adhesion; thus, impaired NO function results in increased leukocyte adhesion. Increased superoxide (derived from NADPH oxidase or uncoupled eNOS) impairs NO bioavailability and leads to impaired vascular relaxation. The figure is based on text.