Multiple mechanisms involved in obesity-induced hypertension

Abstract

Obesity and hypertension are two major cardiovascular risk factors gaining epidemic proportions in our modern world. The interplay between hypertension, obesity and their major detrimental outcome, cardiovascular disease, is multifaceted and can be represented as the three corners of a triangle. Obesity and hypertension both lead to cardiovascular complications. In addition, obesity per se can promote hypertension. In turn, cardiovascular diseases can also predispose to obesity and hypertension. Low levels of physical activity due to a weakened heart promote weight gain. Endothelial, vascular and renal dysfunctions, all consequences of high blood pressure, further worsen hypertension. The loop of mutually amplifying detrimental effects is thus closed: a 'vicious triangle' is established. The association between obesity and hypertension was recognised and described almost a century ago, but the mechanisms that underlie this connection are still not fully understood. Vasoconstriction and sodium retention seem to be the cornerstones of the obesity-hypertension puzzle. However, pathways possibly leading to vasoconstriction and sodium retention are numerous. Evidence has been gathered that hyperleptinaemia, hyperinsulinaemia and elevated free fatty acids may induce sympathetic activation and vasoconstriction. The latter is further potentiated by insulin resistance and endothelial dysfunction. Positive sodium balance and ensuing volume expansion may be due to increased renal tubular sodium reabsorption induced by sympathetic stimulation, insulin or by a hyperactive renin-angiotensin system. All enumerated factors act together toward a state of permanently elevated blood pressure.