The antihypertensive effect of arginine

Abstract

Hypertension is a leading cause of morbidity and mortality worldwide. Individuals with hypertension are at increased risk of 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. Reducing dietary salt is effective in lowering blood pressure in salt-sensitive individuals. Insulin resistance and altered glucose metabolism are common features of hypertension in humans and animal models, with or without salt sensitivity. Altered glucose metabolism leads to increased formation of advanced glycation end products. Insulin resistance is also linked to oxidative stress, and alterations in the nitric oxide pathway and renin angiotensin system. A diet rich in protein containing the semiessential amino acid, arginine, and arginine treatment, lowers blood pressure in humans and in animal models. This may be due to the ability of arginine to improve insulin resistance, decrease advanced glycation end products formation, increase nitric oxide, and decrease levels of angiotensin II and oxidative stress, with improved endothelial cell function and decreased peripheral vascular resistance. The Dietary Approaches to Stop Hypertension (DASH) study demonstrated that the DASH diet, rich in vegetables, fruits and low-fat dairy products; low in fat; and including whole grains, poultry, fish and nuts, lowered blood pressures even more than a typical North American diet with similar reduced sodium content. The DASH diet is rich in protein; the blood pressure-lowering effect of the DASH diet may be due to its higher arginine-containing protein, higher antioxidants and low salt content.

Keywords: Advanced glycation end products; Arginine; Hypertension; Insulin resistance; Nitric oxide; Oxidative stress; Renin angiotensin system.

Figure 1)

Mechanism of salt-sensitive and essential hypertension. AGEs Advanced glycation end products; NO Nitric oxide; RAS Renin angiotensin system

Figure 2)

The interaction of various factors, including arginine, that comprise the complex biochemical network involved in blood pressure regulation. Alterations in any of these factors (eg, insulin resistance, oxidative stress, arginine deficiency) affects the system as a whole and can result in endothelial dysfunction, increased peripheral vascular resistance and hypertension. + Increase; – Decrease; AII Angiotensin II; ACE Angiotensin converting enzyme; ADMA Asymmetrical dimethyl arginine; DDAH Dimethylarginine dimethylamino-hydrolase; NO Nitric oxide; NOS NO synthase; OONO⁻ Peroxynitrite; PRMT Protein methyltransferase; ROS Reactive oxygen species

Figure 3)

Sources and physiological functions of arginine. ATP Adenosine triphosphate

Figure 4)

Mechanism of antihypertensive action of arginine. Arginine improves insulin resistance and decreases advanced glycation end product (AGE) formation, increases nitric oxide production, decreases angiotensin II levels and reduces oxidative stress, resulting in improved endothelial function, and decreased peripheral vascular resistance and blood pressure. ADMA Asymmetrical dimethyl arginine