Post-stroke losartan and captopril treatments arrest hemorrhagic expansion in SHRsp without lowering blood pressure.

We assessed the ability of poststroke losartan and captopril treatment to attenuate hematoma expansion and plasma extravasation after intracerebral hemorrhagic stroke in Kyoto-Wistar stroke-prone hypertensive rats (SHRsp). Cerebrum volume, herniation and surface areas exhibiting new and old hemorrhages and albumin extravasation were measured prior to and after stroke and following 30 and 60 days of post-stroke losartan or captopril treatment in Evans Blue dye perfused brains. Lesion morphology was studied in serial sections. Losartan or captopril treatment initiated at stroke prevented death for 60 days without lowering BP. Stroke onset was associated with the development and subsequent expansion of cerebrum volume, herniation, hematoma and plasma albumin extravasation. Losartan arrested cerebral volume expansion and herniation, and produced the virtual disappearance of hematoma and plasma albumin extravasation after 60 days. Captopril treatment equally attenuated cerebral herniation and hematoma expansion but was less effective in stopping albumin extravasation and allowed cerebrum volume to increase to post-stroke levels after 60 days of treatment. Both treatments resolved hematomas into cortical fluid filled spaces and prevented new hemorrhage formation. We believe that the treatments attenuated death after stroke by inhibiting hemorrhagic expansion through non-pressure related physiological changes mediated by the inhibition of the renin-angiotensin system.

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

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.

Antihypertensive effects of dietary protein and its mechanism.

Hypertension is a leading cause of morbidity and mortality worldwide. Individuals with hypertension are at increased risk of stroke, heart disease and kidney failure. Both genetic and lifestyle factors, particularly diet, have been attributed an important role in the development of hypertension. Reducing dietary sugar and salt intake can help lower blood pressure; similarly, adequate protein intake may also attenuate hypertension. Observational, cross-sectional and longitudinal epidemiological studies, and controlled clinical trials, have documented significant inverse associations between protein intake and blood pressure. Human and animal studies have shown that specific amino acids within proteins may have antihypertensive effects. Cysteine, glutathione (a tripeptide), glutamate and arginine attenuate and prevent alterations that cause hypertension including insulin resistance, decreased nitric oxide bioavailability, altered renin angiotensin system function, increased oxidative stress and formation of advanced glycation end products. Leucine increases protein synthesis in skeletal muscle and improves insulin resistance by modulating hepatic gluconeogenesis. Taurine and tryptophan attenuate sympathetic nervous system activity. Soy protein helps lower blood pressure through its high arginine content and antioxidant activity exhibited by isoflavones. A diet containing an ample amount of protein may be a beneficial lifestyle choice for individuals with hypertension; one example is the Dietary Approaches to Stop Hypertension (DASH) diet, which is low in salt and saturated fat; includes whole grains, lean meat, poultry, fish and nuts; and is rich in vegetables, fruits and low-fat dairy products, which are good sources of antioxidant vitamins, minerals and fibre. Including an adequate supply of soy in the diet should also be encouraged.

Role of methylglyoxal in essential hypertension.

Altered glucose metabolism due to insulin resistance is a common feature of essential hypertension in humans and in animal models. Elevated endogenous aldehydes in genetic (spontaneously hypertensive rats) and acquired (fructose-induced hypertensive rats) models of essential hypertension may be due to increased production of the reactive aldehyde methylglyoxal, resulting from altered glucose metabolism. Excess methylglyoxal binds sulfhydryl groups of membrane proteins, altering calcium channels and increasing cytosolic free Ca(2+) and blood pressure. It has been demonstrated that methylglyoxal, when given in drinking water to Wistar-Kyoto rats, leads to an increase in kidney aldehyde conjugates, cytosolic free Ca(2+) concentration, decreased serum nitric oxide, renal vascular hyperplasia and hypertension. N-acetylcysteine (NAC) in the diet of these animals prevented hypertension and associated biochemical and morphological changes. NAC normalizes blood pressure by directly binding to excess methylglyoxal, thus normalizing Ca(2+) channels, cytosolic Ca(2+) and nitric oxide. NAC also leads to increased levels of tissue glutathione, a storage form of cysteine. Glutathione acts as a cofactor in the enzymatic catabolism of methylglyoxal. Cysteine and other antioxidants, such as vitamins B(6), C and E, and lipoic acid, prevented hypertension and associated biochemical and morphological changes in both genetic and acquired rat models of hypertension. The antihypertensive effect of dietary antioxidants may be due to an increase in tissue cysteine and glutathione, which improves glucose metabolism and decreases tissue methylglyoxal. A diet rich in these antioxidants may be effective in preventing and controlling hypertension in humans.