Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension

Abstract

Oxidative stress and inflammation have recently been linked to endothelial damage in essential hypertension (EH). Activated peripheral polymorphonuclear leukocytes (PMN) damage surrounding tissue by releasing reactive oxygen species (ROS) and proteolytic enzymes before self-necrosis. PMN necrosis further exacerbates inflammation and promotes chemotaxis and PMN recruitment. The number and properties of PMN from untreated EH patients is the focus of the present study. Oxidative stress was assessed by measuring the rate of superoxide anion release from separated, phorbol ester-stimulated PMN and the redox state of plasma glutathione. Inflammation was estimated indirectly by determining PMN number and their in vitro survival. PMN from EH patients (n = 37) released superoxide anion faster (P < .0001) than those of normotensives (NC, n = 37), 17.7 +/- 1.14 v 9.54 +/- 0.51 nmol/10 min/10(6) cells. The redox state of glutathione was twofold higher in EH plasma (P < .02) indicating systemic oxidative stress. PMN survival in vitro correlates linearly with the rate of superoxide release (r2 = 0.60, P < .02) and PMN count of EH patients, although in the normal range, were significantly higher (P < .0001), indicating necrosis and recruitment. Hypertensive plasma significantly reduced NC PMN viability, whereas normal plasma significantly increased EH PMN viability. What our studies show is that EH is accompanied by a primed state PMN that does not correlate with the levels of blood pressure. PMN priming in EH patients reflects an in vivo exposure to a constant stimulus ending in oxidative stress, increased self-necrosis, and cell recruitment. Oxidative stress and inflammation will result in endothelial damage and atherosclerosis in the long run.

An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension

“…Plasma Creactive protein has been shown to be an independent risk factor for hypertension, 32 and PMNL count in peripheral blood and increased superoxide release contributes to hypertension. 33 In the animal model, the activation of NF-kB is increased in numerous tissues in stroke-porne spontaneous hypertension (SHRsp) rats compared with Sprague-Dawley (SD) rats. 34 NF-kB promotes proinflammatory genes or induces apoptosis in many organs.…”

Mechanisms of H2O2-induced oxidative stress in endothelial cells

“…Inflammation has been implicated in cardiovascular disease, notably in atherosclerosis (Liuzzo 2001;Eldika et al 2004) and essential hypertension (Kristal et al 1998). Inflammation is associated with a shift in endothelial cell phenotype, resulting in increased expression of inflammatory mediators, cytokines, and iNOS activation (Granger et al 2004).…”

Cyclooxygenase-2 Inhibitors Attenuate Angiotensin II–Induced Oxidative Stress, Hypertension, and Cardiac Hypertrophy in Rats

“…Numerous clinical and experimental evidences indicate that oxidative stress plays an important pathogenetic role in cardiovascular diseases, including atherosclerosis 1 and hypertension. 2,3 Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the cyclooxygenase (COX) activity, which converts arachidonic acid to various prostaglandins and thromboxanes. 4 This enzyme is found in 2 isoforms: the constitutive isoform, COX-1, and the inducible isoform, COX-2.…”