The Renin Angiotensin Aldosterone System in Hypertension: Roles of Insulin Resistance and Oxidative Stress

Abstract

The relationship between HTNand other components of the CMSis complex. However, there is growing evidence that enhanced activation of the RAAS is a key factor in the development of endothelial dysfunction and HTN. Insulin resistance is induced by activation of the RAAS and resulting increases in ROS. This insulin resistance occurs in cardiovascular tissue and in tissues traditionally considered as targets for the action of insulin, such as muscle and liver. Indeed, there is a mounting body of evidence that the resultant insulin resistance in cardiovascular tissue and kidneys contributes to the development of endothelial dysfunction, HTN, atherosclerosis, CKD, and CVD.77 RAAS-associated signaling by way of the AT1R and MR, triggers tissue activation of the NADPH oxidase enzymatic activation and increased production of ROS. Oxidative stress in cardiovascular tissue is derived from both NADPH oxidase and mitochondrial generation of ROS, and is central to the development of insulin resistance, endothelial dysfunction, HTN, and atherosclerosis. Pharmacologic blockade of the RAAS not only improves blood pressure, but alsohas a beneficial impact on inflammation, oxidative stress, insulin sensitivity, and glucose homeostasis. Several strategies are available for RAAS blockade, including ACE inhibitors, ARBs, and MR blockers, which have been proven in the clinical trials to result in improved CVD and CKD outcomes. New research in these areas will allow for a better understanding of the relationship between HTN, insulin resistance, and activation of the RAAS, which could result in newer alternatives for a more comprehensive management of HTN in the setting of the CMS..

Sex-dependent hepatic transcripts and metabolites in the development of glucose intolerance and insulin resistance in Zucker diabetic fatty rats

“…Hepatic angiotensinogen is part of the reninangiotensin-aldosterone system, which functions in the homeostatic control of arterial pressure, tissue perfusion and extracellular volume (Manrique et al 2009). Using mZDF rats, angiotensinogen was recently shown to be induced in mesangial cells via ROS/ ERK/JNK pathways (Ohashi et al 2010), and similar mechanisms might be operating in the liver.…”

Triglyceride-Based Screening Tests Fail to Recognize Cardiometabolic Disease in African Immigrant and African-American Men

“…To overcome this deficit, we used proven markers of cardiometabolic risk, specifically insulin resistance, prediabetes, diabetes, and metabolic triad. [23][24][25][26]42 Second, only men were enrolled. Because TG levels are even lower in black women than men, it is likely that the inability of TG levels to predict cardiometabolic disease would be magnified in women.…”

“…Blood samples for the measurement of glucose and insulin levels were obtained at -10, -5, -1, 1, 2, 3,4,5,6,7,8,10,12,14,16,19,22,23,24,25,27,30,40,50,60,70,80,90, 100, 120, 150, and 180 min. IM-FSIGT data were used to calculate the insulin sensitivity index (S I ) and acute insulin response to glucose (AIRg).…”

“…[12][13][14]22 Therefore, cardiometabolic disease in African Americans develops due to TG-independent pathways such as inflammation, endothelial dysfunction, and hypertension. 23,24 Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. To determine the efficacy of TG-based screening tests in men of African descent, we studied the association between hypertriglyceridemia (TG ‡ 150 mg/dL) and cardiometabolic disease in both African immigrants to the United States and in African Americans.…”

A Comparative Study of Olmesartan and Valsartan on Insulin Sensitivity in Hypertensive Patients with Diabetes Mellitus or Impaired Glucose Tolerance (OVIS Study)

“…Furthermore, these effects may be due to blocking the oxidative stress and the reduction of adiponectin level [36]. Telmisartan and irbesartan have a partial agonist action of PPARγ [30] and are expected to have beneficial effects on insulin resistance by increasing adiponectin levels than the other ARBs without such action.…”