Early Changes in Renal Vasculature in Prehypertension
The microvasculature of the kidney is one of the first culprits of an increase in blood pressure. The sensitive structures in the cortex and in the papilla of the kidney are affected in several ways. The endothelial cells are challenged by an increase in circulating and locally released hormones such as angiotensin II, sympathetic activition and endothelins. In addition, the local disturbance in blood flow activates the endothelial cells. At the same time a decrease in oxygen consumption and less NO together with hemodynamic alterations and metabolic changes leads to “endothelial dysfunction.” The activated endothelial cells express more adhesion molecules, release proteases, and increase the expression of cytokines. All these factors lead on the one hand to increased adhesion of circulating blood cells such as monocytes which infiltrate the interstitial tissue of the kidney early. In addition, the release of proteases leads to a loss of glycocalyx and a changed behavior of these surface molecules. The loss of glycocalyx plays not only a role in adhesion and inflammation but also changes the storage capacities of the endothelium for salt and water. Lastly, the loss of growth factors such as VEGF leads to capillary rarefaction, endothelial dedifferentiation, and therefore to a loss of nephrons. Altogether these early mechanisms in hypertension result in interstitial injury with rarefaction of vasculature and nephrons. Therefore the remaining nephrons are exposed to more work load, altered metabolism, and enhanced sensitivity to circulating hormones. Clinically these early changes are not yet clinically detectable but provide the ground work for the renal damage in hypertensive patients in the future.
KeywordsEndothelium Glycocalyx Adhesion molecules Monocytes Inflammation VEGF Capillary rarefaction Nephron loss Interstitial inflammation
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