Role of the immune system in hypertension: modulation by dietary antioxidants

Abstract

Hypertension is a major health problem worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease, and kidney failure. Although the etiology of essential hypertension has a genetic component, lifestyle factors such as diet play an important role. Insulin resistance is a common feature of hypertension in both humans and animal models affecting glucose and lipid metabolism producing excess aldehydes including methylglyoxal. These aldehydes react with proteins to form conjugates called advanced glycation end products (AGEs). This alters protein structure and function and can affect vascular and immune cells leading to their activation and secretion of inflammatory cytokines. AGEs also act via receptors for advanced glycation end products on these cells altering the function of antioxidant and metabolic enzymes, and ion channels. This results in an increase in cytosolic free calcium, decrease in nitric oxide, endothelial dysfunction, oxidative stress, peripheral vascular resistance, and infiltration of vascular and kidney tissue with inflammatory cells leading to hypertension. Supplementation with dietary antioxidants including vitamins C, E, or B(6), thiols such as cysteine and lipoic acid, have been shown to lower blood pressure and plasma inflammatory cytokines in animal models and humans with essential hypertension. A well-balanced diet rich in antioxidants that includes vegetables, fruits, low fat dairy products, low salt, and includes whole grains, poultry, fish and nuts, lowers blood pressure and vascular inflammation. These antioxidants may achieve their antihypertensive and anti-inflammatory/immunomodulatory effects by reducing AGEs and improving insulin resistance and associated alterations. Dietary supplementation with antioxidants may be a beneficial, inexpensive, front-line alterative treatment modality for hypertension.

Keywords: Hypertension; T cells; advanced glycation end products; dietary antioxidants; immune system; inflammatory cytokines; insulin resistance; macrophages; oxidative stress; receptors for advanced glycation end products; renal damage; renin-angiotensin system.

Figure 1

Mechanism of essential hypertension. Insulin resistance, due to genetic and lifestyle factors, leads to altered glucose and lipid metabolism with an increase in methylglyoxal and other reactive aldehydes. Excess aldehydes form advanced glycation end products (AGEs) which leads to oxidative stress and activation of the immune system. This leads to decreased nitric oxide (NO), endothelial dysfunction, inflammation, increased inflammatory cytokines, cytosolic free calcium, peripheral vascular resistance, and hypertension. Increased inflammatory cytokines may also lead to insulin resistance. RAS, renin-angiotensin system.

Figure 2

Mechanism of antihypertensive and immunomodulatory action of dietary antioxidants. Antioxidants work directly to neutralize reactive oxygen species (ROS) and indirectly by improving insulin resistance and decreasing aldehyde and advanced glycation end product (AGE) formation. This leads to normalization of the immune system, decreased inflammation, improved endothelial function, and decreased blood pressure. NO, nitric oxide.