Hypertension Treatment Medical Nutrition Therapy Encourage weight loss for all overweight individuals, even modest weight lose lowers blood pressure. Physical activity and behavior modifications are important for weight loss and maintenance. Adjust mix of carbohydrates, protein, and fat to meet metabolic goals and preferences; customize nutrition counseling based on ApoE genotype. Is it time to begin restricting fructose in the diet? Limit alcohol intake. Promote smoking cessation. US Endocrine Review 2006;1:2-5

Medical Nutrition Therapy Critically Based on ApoE Genotype 1.Arterioscler Thromb Vasc Biol 2000;20:1990-199 2. Am J Clin Nutr 2003;77:1098-1111 3. J Nutr 2004;134:2517-2522 4. Am J Clin Nutr 2001;73:736-745

Dietary Fructose Intake ↑ Glu5 Transporter Facilitating Fructose Absorption Localization of Glut2 and Glut5 in jejunum and their regulation in response to increased dietary fructose intake. Glut5 which only transports fructose but not glucose resides in the apical membrane at basal state (a) and is activated in response to increased dietary fructose intake (b). Glut2 which can transport both glucose and fructose is expressed in the cytoplasm and on basolateral membrane at basal state (a) and is recruited to the apical membrane in the presence of increased dietary fructose or glucose intake. Int J Nephrol, Volume 2011, Article ID 392708, 8 pages

High Fructose Diet ↑ Sodium and Chloride Absorption -> Hypertension The proposed role of salt transporters in the development of hypertension following a high fructose diet. NHE3, sodium-hydrogen exchanger 3, PAT1, putative anion transporter 1. The increased salt absorption by the intestine and decreased salt excretion by the kidney observed in fructose fed rodents are believed to contribute to hypertension There are three transporters that are up-regulated by fructose in the small intestine and proximal renal tubule. The first is the major fructose transporter GLUT5, which facilitates fructose Absorption. The second is the sodium-hydrogen exchanger 3 (NHE3), a sodium transporter, and the third is the putative anion transporter 1 (PAT1), a chloride transporter [19–21]. 19. Dietary fructose, salt absorption and hypertension in metabolic syndrome: towards a new paradigm. Acta Physiol 2011; 201:55–62. 20. The role of salt in the pathogenesis of fructose induced hypertension. Int J Nephrol 2011; 392708, 392708pp. 21. Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and GLUT5. Kidney Int 2008; 74:438–447. NHE3, sodium-hydrogen exchanger 3, PAT1, putative anion transporter 1 J Hypertens 2015;33:912–920

High Fructose Diet Increases Sympathetic Nervous System Activations -> Hypertension The proposed role of the sympathetic nervous system in the development of hypertension following a high fructose diet. J Hypertens 2015;33:912–920

Sugar Not Salt Drives Hypertension- Are We Looking at the Wrong White Crystal! Hypertensive mechanisms of fructose. Arrows represent direct effects, or indirect effects through intermediates, which is not shown for simplicity. NO, nitric oxide; RAS, renin-angiotensin system; RNS, reactive nitrogen species; ROS, reactive oxygen species. Open Heart 2014;1:e000167

High Salt Diet Stimulates Fructose Production in the Liver Glucose ↑ ↑ High Salt Diet Increases Serum Osmolarity Increases Aldose Reductase ↑ ↑ ↑ TonEBP* Fructose *Tonicity-responsive enhancer binding-protein