Mechanisms of disease: oxidative stress and inflammation in the pathogenesis of hypertension.
Animal studies have shown that oxidative stress and renal tubulointerstitial inflammation are associated with, and have major roles in, the pathogenesis of hypertension. This view is supported by the observations that alleviation of oxidative stress and renal tubulointerstitial inflammation reduce arterial pressure in animal models. Conversely, hypertension has been shown to cause oxidative stress and inflammation in renal and cardiovascular tissues in experimental animals. Taken together, these observations indicate that oxidative stress, inflammation and arterial hypertension participate in a self-perpetuating cycle which, if not interrupted, can lead to progressive cardiovascular disease and renal complications. These events usually occur in an insidious and asymptomatic manner over an extended period following the onset of hypertension. Severe target organ injury can, however, occasionally occur precipitously in the course of malignant or accelerated hypertension. Given the high degree of heterogeneity of hypertensive disorders, the factor(s) initiating the vicious cycle described vary considerably in different forms of hypertension. For instance, oxidative stress in the kidney and vascular tissue is the primary mediator in the pathogenesis of angiotensin-induced, and perhaps lead-induced, hypertension. By contrast, increased arterial pressure is probably the initiating trigger in salt-sensitive hypertension. Although the initiating factor might vary between hypertensive disorders, according to the proposed model, the three components of the cycle eventually coalesce in all forms of hypertension.
Vaziri
Nosratola D
ND
Division of Nephrology and Hypertension, at the University of California Irvine, Irvine, CA, USA. ndvaziri@uci.edu
Rodríguez-Iturbe
Bernardo
B
D000818:Animals; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*