The antihypertensive effect of cysteine

Abstract

Hypertension is a leading cause of morbidity and mortality worldwide. Individuals with hypertension are at an increased risk for stroke, heart disease and kidney failure. Essential hypertension results from a combination of genetic and lifestyle factors. One such lifestyle factor is diet, and its role in the control of blood pressure has come under much scrutiny. Just as increased salt and sugar are known to elevate blood pressure, other dietary factors may have antihypertensive effects. Studies including the Optimal Macronutrient Intake to Prevent Heart Disease (OmniHeart) study, Multiple Risk Factor Intervention Trial (MRFIT), International Study of Salt and Blood Pressure (INTERSALT) and Dietary Approaches to Stop Hypertension (DASH) study have demonstrated an inverse relationship between dietary protein and blood pressure. One component of dietary protein that may partially account for its antihypertensive effect is the nonessential amino acid cysteine. Studies in hypertensive humans and animal models of hypertension have shown that N-acetylcysteine, a stable cysteine analogue, lowers blood pressure, which substantiates this idea. Cysteine may exert its antihypertensive effects directly or through its storage form, glutathione, by decreasing oxidative stress, improving insulin resistance and glucose metabolism, lowering advanced glycation end products, and modulating levels of nitric oxide and other vasoactive molecules. Therefore, adopting a balanced diet containing cysteine-rich proteins may be a beneficial lifestyle choice for individuals with hypertension. An example of such a diet is the DASH diet, which is low in salt and saturated fat; includes whole grains, poultry, fish and nuts; and is rich in vegetables, fruits and low-fat dairy products.

Figure 1)

Mechanism of hypertension. Hypertension develops from a combination of genetic and lifestyle factors such as diet. A diet high in salt or sugar, and low in antioxidants and protein, has been implicated in hypertension. Increased oxidative stress and a decreased bioavailability of nitric oxide (NO); insulin resistance and altered glucose metabolism with an increase in advanced glycation end products (AGEs); activation of the renin-angiotensin system (RAS); and damage to kidneys resulting in altered renal function are all mechanisms that contribute to the development of hypertension

Figure 2)

Metabolic formation of cysteine. Methionine, an essential amino acid obtained through diet, is converted via an enzymatic pathway to the thiol-containing amino acid cysteine. This pathway includes the vitamin B₆-dependent enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). N-acetylcysteine (NAC), a cysteine analogue also available in the diet, is deacylated to cysteine primarily in the kidneys. Cysteine may be further converted to the ubiquitious antioxidant glutathione (GSH) or enzymatically converted into the vasoactive molecule H₂S via CBS

Figure 3)

Chemical structures of cysteine and reduced glutathione. Free sulfhydryl groups of these molecules contribute to much of their biological activity

Figure 4)

Sources and antihypertensive actions of cysteine and glutathione (GSH). Cysteine is derived from dietary methionine, cysteine or N-acetylcysteine. It exerts its antihypertensive action directly, or indirectly through its storage form GSH. Cysteine decreases blood pressure by lowering oxidative stress, improving insulin resistance, altering glucose metabolism to lower advanced glycation end products (AGEs), improving the bioavailability of nitric oxide (NO), modulating other vasoactive molecules such as angiotensin II and H₂S, and improving renal function