![]() All three of these are closely inter-related and establish a deadly combination that leads to ED, vascular smooth muscle and cardiac dysfunction, hypertension, vascular disease, atherosclerosis and CVD. ![]() Oxidative stress (ROS and RNS), inflammation (increased expression of redox-sensitive pro-inflammatory genes, CAMs and recruitment migration and infiltration of circulating cells) and autoimmune vascular dysfunction (T cells and B cells) are the primary pathophysiologic and functional mechanisms that induce vascular disease (Figure (Figure5). Vascular biology assumes a pivotal role in the initiation and perpetuation of hypertension and cardiovascular TOD. In particular, the high Na +/K + ratio of modern diets has contributed to hypertension, CVA, CHD, MI, CHF and renal disease as have the relatively low intake of omega-3 PUFA, increase in omega-6 PUFA, saturated fat and trans fatty acids. Poor nutrition, coupled with obesity and a sedentary lifestyle have resulted in an exponential increase in nutritionally-related diseases. Reduction in nitric oxide bioavailability, increase in angiotensin II and endothelin coupled with endothelial activation initiate the vascular and cardiac dysfunction and hypertension. The macronutrient and micronutrient variations, oxidative stress from radical oxygen species (ROS) and radical nitrogen species (RNS) and inflammatory mediators such as cell adhesion molecules (CAMs), cytokines, signaling molecules and autoimmune vascular dysfunction of T cells and B cells, contribute to the higher incidence of hypertension and other cardiovascular diseases through complex nutrient-gene interactions, epigenetic and nutrient-caveolae interactions and nutrient reactions with pattern recognition receptors in the endothelium (Figure (Figure4). The human genetic makeup is 99.9% that of our Paleolithic ancestors, yet our nutritional, vitamin and mineral intakes are vastly different. Endothelial activation with ED and vascular smooth muscle dysfunction (VSMD) initiate and perpetuate essential hypertension. Nutrient-gene interactions, subsequent gene expression, epigenetics, oxidative stress, inflammation and autoimmune vascular dysfunction have positive or negative influences on vascular biology in humans. Macronutrients and micronutrients are crucial in the regulation of blood pressure (BP) and subsequent target organ damage (TOD). Hypertension is a consequence of the interaction of genetics and environment. Hypertension may be a hemodynamic marker of injured endothelium and vascular smooth muscle related to finite responses of inflammation, oxidative stress and immune dysfunction of the arteries leading to ED, vascular and cardiac smooth muscle dysfunction, loss of arterial elasticity with reduced arterial compliance and increased systemic vascular resistance. Various insults that damage the endothelium, lead to endothelial dysfunction (ED) and may induce hypertension and other cardiovascular diseases. ![]() The endothelium is in a strategic location between the blood and the vascular smooth muscle and secretes various substances to maintain vascular homeostasis and health (Figures (Figures2 2 and and3). Vascular disease is a balance between vascular injury and repair (Figure (Figure1).
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