Abstract-Angiotensin (Ang) II induces hypertension by mechanisms mediated in part by adaptive immunity and T effector lymphocytes. T regulatory lymphocytes (Tregs) suppress T effector lymphocytes. We questioned whether Treg adoptive transfer would blunt Ang II-induced hypertension and vascular injury. Ten-to 12-week-old male C57BL/6 mice were injected IV with 3ϫ10 5 Treg (CD4 ϩ CD25 ϩ ) or T effector (CD4 ϩ CD25 Ϫ ) cells, 3 times at 2-week intervals, and then infused or not with Ang II (1 g/kg per minute, SC) for 14 days. Ang II increased systolic blood pressure by 43 mm Hg (PϽ0.05), NADPH oxidase activity 1.5-fold in aorta and 1.8-fold in the heart (PϽ0.05), impaired acetylcholine vasodilatory responses by 70% compared with control (PϽ0.05), and increased vascular stiffness (PϽ0.001), mesenteric artery vascular cell adhesion molecule expression (2-fold; PϽ0.05), and aortic macrophage and T-cell infiltration (PϽ0.001). All of the above were prevented by Treg but not T effector adoptive transfer. Ang II caused a 43% decrease in

Aldosterone mediates actions of the renin-angiotensin-aldosterone system inducing hypertension, oxidative stress, and vascular inflammation. Recently, we showed that angiotensin II-induced hypertension and vascular damage are mediated at least in part by macrophages and T-helper effector lymphocytes. Adoptive transfer of suppressor T-regulatory lymphocytes (Tregs) prevented angiotensin II action. We hypothesized that Treg adoptive transfer would blunt aldosterone-induced hypertension and vascular damage. Thirteen to 15-week-old male C57BL/6 mice were injected intravenously at 1-week intervals with 3×10(5) CD4(+)CD25(+) cells (representing Treg) or control CD4(+)CD25(-) cells and then infused or not for 14 days with aldosterone (600 μg/kg per day, SC) while receiving 1% saline to drink. Aldosterone induced a small but sustained increase in blood pressure (P<0.001), decreased vasodilatory responses to acetylcholine by 66% (P<0.001), increased both media:lumen ratio (P<0.001) and media cross-sectional area of resistance arteries by 60% (P<0.05), and increased NADPH oxidase activity 2-fold in aorta (P<0.001), kidney and heart (P<0.05), and aortic superoxide production. As well, aldosterone enhanced aortic and renal cortex macrophage infiltration and aortic T-cell infiltration (all P<0.05), and tended to decrease Treg in the renal cortex. Treg adoptive transfer prevented all of the vascular and renal effects induced by aldosterone. Adoptive transfer of CD4(+)CD25(-) cells exacerbated aldosterone effects except endothelial dysfunction and increases in media:lumen ratio of resistance arteries. Thus, Tregs suppress aldosterone-mediated vascular injury, in part through effects on innate and adaptive immunity, suggesting that aldosterone-induced vascular damage could be prevented by an immunomodulatory approach.

Attention is growing for a potential role of magnesium in the pathoetiology of cardiovascular disease. Magnesium modulates mechanical, electrical and structural functions of cardiac and vascular cells, and small changes in extracellular magnesium levels and/or intracellular free magnesium concentration may have significant effects on cardiac excitability and on vascular tone, contractility and reactivity. Thus, magnesium may be important in the physiological regulation of blood pressure whereas alterations in cellular magnesium metabolism could contribute to the pathogenesis of blood pressure elevation. Although most epidemiological and experimental studies support a pathological role for magnesium in the etiology and development of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of essential hypertension is unclear. The present review discusses the molecular, biochemical, physiological and pharmacological roles of magnesium in the regulation of vascular function and blood pressure and introduces novel concepts relating to magnesium as a second messenger in intracellular signaling in cardiovascular cells. In addition, alterations in magnesium regulation in experimental and clinical hypertension and the potential antihypertensive therapeutic effects of magnesium are addressed.

Humans are not programmed to be inactive. The combination of both accelerated sedentary lifestyle and constant food availability disturbs ancient metabolic processes leading to excessive storage of energy in tissue, dyslipidaemia and insulin resistance. As a consequence, the prevalence of Type 2 diabetes, obesity and the metabolic syndrome has increased significantly over the last 30 years. A low level of physical activity and decreased daily energy expenditure contribute to the increased risk of cardiovascular morbidity and mortality following atherosclerotic vascular damage. Physical inactivity leads to the accumulation of visceral fat and consequently the activation of the oxidative stress/inflammation cascade, which promotes the development of atherosclerosis. Considering physical activity as a 'natural' programmed state, it is assumed that it possesses atheroprotective properties. Exercise prevents plaque development and induces the regression of coronary stenosis. Furthermore, experimental studies have revealed that exercise prevents the conversion of plaques into a vulnerable phenotype, thus preventing the appearance of fatal lesions. Exercise promotes atheroprotection possibly by reducing or preventing oxidative stress and inflammation through at least two distinct pathways. Exercise, through laminar shear stress activation, down-regulates endothelial AT1R (angiotensin II type 1 receptor) expression, leading to decreases in NADPH oxidase activity and superoxide anion production, which in turn decreases ROS (reactive oxygen species) generation, and preserves endothelial NO bioavailability and its protective anti-atherogenic effects. Contracting skeletal muscle now emerges as a new organ that releases anti-inflammatory cytokines, such as IL-6 (interleukin-6). IL-6 inhibits TNF-α (tumour necrosis factor-α) production in adipose tissue and macrophages. The down-regulation of TNF-α induced by skeletal-muscle-derived IL-6 may also participate in mediating the atheroprotective effect of physical activity.

Pharmacological inhibition of arginase in adult spontaneously hypertensive rats decreases blood pressure and improves the reactivity of resistance vessels. These data represent in-vivo argument in favor of selective arginase inhibition as a new therapeutic strategy against hypertension.

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The mechanical properties of the wall of isolated perfused arterial segments of mesenteric small arteries from 17-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY) were investigated. Third-order branches of mesenteric arteries were mounted in a pressure myograph chamber and pressurized from 1 to 140 mm Hg. Under isobaric conditions, the outer diameter and the lumen of small arteries studied were smaller in SHR than in WKY, whereas media width, media cross-sectional area and media-lumen ratio were greater in SHR. Under passive conditions, the total change in internal and external diameter in response to increasing intravascular pressure was smaller in arteries from SHR. Incremental distensibility was significantly lower in arteries of SHR at intravascular pressures between 1 and 40 mm Hg, but was significantly greater between pressures of 40–100 mm Hg. Wall stress generated by intravascular pressure was significantly smaller in arteries from SHR. As a function of wall strain (under isometric conditions), stress and incremental elastic modulus were shifted to the left in SHR vessels. Under isobaric conditions or in relation to wall stress, the slope of elastic modulus was smaller in SHR. This decrease in elastic modulus may confer additional elasticity to the vascular wall of resistance arteries from SHR. The presence of a greater distensibility at physiological levels of intravascular pressure and decreased incremental elastic modulus indicates that the changes in the structure of small mesenteric arteries in SHR can be defined as the result of a combination of eutrophic and hypertrophic remodeling.

Metabolic syndrome induced by HFD is reversed by exercise and diet modification. It is demonstrated that exercise training induces these beneficial effects without the requirement for dietary modification, and these beneficial effects may be mediated by shear stress-induced Akt/eNOS pathway activation. Thus, exercise may be an effective strategy to reverse almost all the atherosclerotic risk factors linked to obesity, particularly in the vasculature.