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Hypothesis: The role of acquired tubulointerstitial disease in the pathogenesis of salt-dependent hypertension

1997; Elsevier BV; Volume: 52; Issue: 5 Linguagem: Inglês

10.1038/ki.1997.442

1523-1755

Richard J. Johnson, George F. Schreiner,

Blood Pressure and Hypertension Studies

We present a new hypothesis to explain the development of salt-dependent hypertension in humans. We propose that hypertension has two phases: an early phase in which elevations in blood pressure (BP) are mainly episodic and are mediated by a hyperactive sympathetic nervous or renin-angiotensin system, and a second phase in which BP is persistently elevated and that is primarily mediated by an impaired ability of the kidney to excrete salt (NaCl). We propose that the transition from the first phase to the second occurs as a consequence of catecholamine-induced elevations in BP that preferentially damage regions of the kidney (juxtamedullary and medullary regions) that do not autoregulate well to changes in renal perfusion pressure. The catecholamine response is associated with both an increase in peritubular capillary pressure and a reduction in peritubular capillary plasma flow, resulting in injury to the peritubular capillaries with ischemia to the tubules and interstitium. The local injury triggers the release or activation (angiotensin II, adenosine, renal sympathetic nerves) or inhibition (nitric oxide, prostaglandins, dopamine) of vasoactive mediators that further augment ischemia and result in abnormal tubuloglomerular feedback and enhanced NaCl reabsorption. The peritubular capillary injury with rarefaction simultaneously blunts the pressure natriuresis mechanism. The combined effect of enhanced tubuloglomerular feedback and impaired pressure natriuresis results in a defect in NaCl excretion which, on the exposure to salt, results in the development of persistent hypertension. Evidence is provided to suggest that this may be the major mechanism for the development of salt-dependent hypertension, and particularly for the hypertension associated with blacks, aging and obesity. Thus, essential hypertension may be a type of acquired tubulointerstitial renal disease.