Salt-sensitive hypertension develops after short-term exposure to angiotensin II

We hypothesized that short-term exposure to angiotensin II (Ang II) could r esult in structural and functional changes in the kidney that would favor s odium retention and the development of sustained hypertension. To test this hypothesis, rats were exposed to presser doses (435 ng.kg(-1).min(-1)) of Ang II for 2 weeks. The infusion of Ang II was associated with acute hypert ension, renal dysfunction, proteinuria, and focal tubulointerstitial and va scular damage. At sites of the tubulointerstitial damage, there was a reduc tion in peritubular capillary endothelial cell staining. By use of immunost aining, 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 t he medulla. When the Ang II infusion ended, the rats became normotensive an d renal function returned toward normal. However, exposure of the rats to h igh 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 t o 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 hy pertension induced by transient exposure to presser doses of Ang II. The me chanism 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 loa d.