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Mechanisms of Disease: oxidative stress and inflammation in the pathogenesis of hypertension

Abstract

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.

Key Points

  • Oxidative stress, inflammation and arterial hypertension participate in a self-perpetuating cycle that can lead to progressive cardiovascular and renal disease

  • The initiating pathogenic factor in this cycle differs in different forms of hypertension

  • Therapeutic strategies should aim to reduce production of reactive oxygen species rather than involving mere administration of antioxidant agents

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Figure 1: The self-perpetuating cycle involving oxidative stress and inflammation in the pathogenesis of hypertension.
Figure 2: Interplay between tubulointerstitial inflammation, the intrarenal renin–angiotensin system and oxidative stress in the hypertensive kidney.
Figure 3: Effect of oxidative stress on nitric oxide metabolism in the kidney, brain and cardiovascular tissues, and its impact on arterial blood pressure.
Figure 4: The role of renal tubulointerstitial inflammation in pathogenesis of salt-sensitive hypertension and hypertension.

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Acknowledgements

Dr Vaziri's work was partially supported by a grant from Heart, Lung and Blood Institute (H27485). Research in Dr Rodríguez-Iturbe's laboratory is supported by FONACIT Grant F-2005000283.

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Correspondence to Nosratola D Vaziri.

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Vaziri, N., Rodríguez-Iturbe, B. Mechanisms of Disease: oxidative stress and inflammation in the pathogenesis of hypertension. Nat Rev Nephrol 2, 582–593 (2006). https://doi.org/10.1038/ncpneph0283

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