Endothelial dysfunction and the kidney: emerging risk factors for renal insufficiency and cardiovascular outcomes in essential hypertension

Abstract

Renal insufficiency in essential hypertension represents the expression of a medium- and small-size arteriolopathy characterized by intimal hyperplasia, hyalinosis, and smooth muscle cell hypertrophy (nephroangiosclerosis). Because in animal models endothelial dysfunction plays a role in this alteration, nephroangiosclerosis and the attendant renal insufficiency may be the expression of a systemic dysfunction of vascular endothelium. Endothelial function in the kidney vasculature of hypertensive individuals has been investigated little because studies on the hemodynamic response of the kidney to nitric oxide activation and blockade are laborious to perform. There is no direct proof that endothelial dysfunction in the forearm or in the coronary circulation is paralleled by a similar hemodynamic dysfunction in the kidney. A recent study in a large population of patients with essential hypertension showed that, independent of other risk factors, the GFR in these patients is strongly related to the forearm blood flow response to acetyl choline (an established test of endothelial function). Furthermore, in this study, C-reactive protein was inversely related to the GFR and with the vasodilatory response to acetyl choline, pointing to inflammation as a likely mechanism to explain the association between endothelial dysfunction and impaired renal function in essential hypertension. A dysfunctional endothelium may represent a critical link accounting for the risk for both renal impairment and cardiovascular complications in essential hypertension.