Renal uptake of circulating angiotensin II in Val5-angiotensin II infused rats is mediated by AT1 receptor

Previous studies have demonstrated that augmentation of intrarenal angiotensin II (ANG II) levels during ANG II induced hypertension involves both endogenous formation and accumulation of circulating ANG II. The present work extends these findings and determines whether accumulation of infused ANG II in the kidney requires AT(1) receptor activation by using Val(5)-ANG II as the infused peptide. Male Sprague-Dawley rats were uninephrectomized and divided into three groups: control (n = 6), Val(5)-ANG II (exogenous form) infused (n = 8), and Val(5)-ANG II infused rats treated with losartan (n = 8). Val(5)-ANG II, which has the same biological and immunoreactive properties as endogenous ANG II, was infused at 40 ng/min via an osmotic minipump implanted subcutaneously. By day 12, systolic blood pressure (SBP) increased significantly in Val(5)-ANG II infused rats (197 +/- 7 mm Hg). As previously shown, the development of hypertension in ANG II infused rats was prevented by losartan treatment. Blood and kidney samples were harvested, subjected to HPLC to separate Val(5)-ANG II (exogenous) from Ile(5)-ANG II (endogenous) and the fractions were measured by radioimmunoassay. In the Val(5)-ANG II infused rats treated with losartan, total plasma ANG II levels were elevated to a greater extent than in rats not treated with losartan (289 +/- 20 v, 119 +/- 14 fmol/mL). However, losartan markedly decreased by 88% the enhancement of intrarenal Val(5)-ANG II content that occurred in the rats infused with Val(5)-ANG II alone. These results demonstrate that AT(1) receptor blockade markedly reduces the intrarenal uptake of circulating ANG II that occurs in ANG II induced hypertension. (C) 1998 American Journal of Hypertension, Ltd.