(Hypertension. 1999;33:1013-1019.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Salt-Sensitive Hypertension Develops After Short-Term Exposure to Angiotensin II
From the Division of Nephrology, Department of Medicine (K.L.G., S.S., R.J.J.)and Department of Pathology (D.L., P.P., S.M.S.), University of Washington Medical Center, Seattle, Wash.
Correspondence to Richard J. Johnson, Division of Nephrology, Box 356521, BB-1257 HSB, University of Washington Medical Center, 1959 Pacific St, Seattle, WA 98195.
Abstract—We hypothesized that short-term exposure to angiotensin II (Ang II) could result in structural and functional changes in the kidney that would favor sodium retention and the development of sustained hypertension. To test this hypothesis, rats were exposed to pressor doses (435 ng · kg-1 · min-1) of Ang II for 2 weeks. The infusion of Ang II was associated with acute hypertension, renal dysfunction, proteinuria, and focal tubulointerstitial and vascular damage. At sites of the tubulointerstitial damage, there was a reduction in peritubular capillary endothelial cell staining. By use of immunostaining, we found focal loss of endothelial nitric oxide synthase (eNOS) in the peritubular capillaries at sites of injury and a generalized reduction in eNOS in collecting ducts, thin loops of Henle, and vascular bundles in the medulla. When the Ang II infusion ended, the rats became normotensive and renal function returned toward normal. However, exposure of the rats to high salt diet (4% NaCl) resulted in the redevelopment of hypertension after 3 to 4 weeks. Rats maintained on a high salt diet with no prior exposure to Ang II and rats placed on low salt diet (0.1% NaCl) after exposure to Ang II remained normotensive. Thus, we report a new model of salt-sensitive hypertension induced by transient exposure to pressor doses of Ang II. The mechanism may relate to microvascular injury with peritubular capillary loss coupled with functional changes, such as a loss in intrarenal nitric oxide formation, that could alter the ability of the kidney to excrete a salt load.
Key Words: angiotensin II • nitric oxide • capillaries, peritubular • hypertension, sodium-dependent
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