Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Hydronephrosis causes salt-sensitive hypertension in rats Mattias Carlstro ¨m a,  , Nils Wa ˚ hlin a,  , Johan Sa ¨ llstro ¨m a , Ole Skøtt b , Russell Brown a and A. Erik G. Persson a Background Hypertension is a common disease in the Western world and approximately 5% of all cases are secondary to kidney malfunction. It is not clear whether unilateral hydronephrosis due to partial obstruction affects blood pressure. Aim The aim of this study was to determine whether hypertension develops and to investigate the effects of different salt diets on the blood pressure in hydronephrotic animals. Methods Unilateral partial ureteral obstruction was created in 3-week-old Sprague–Dawley rats. A telemetric device was implanted 4–6 weeks later and blood pressure was measured on normal, low- and high-salt diets. Plasma samples were collected on all diets for renin analysis. Results All hydronephrotic animals developed hypertension that correlated to the degree of hydronephrosis. The blood pressure increased slowly with time and was salt sensitive. In severe hydronephrosis, blood pressure increased from 118 W 5 mmHg on low salt to 140 W 6 mmHg on high salt intake, compared to control levels of 82 W 2 and 84 W 2 mmHg, respectively. Plasma renin concentration was increased in the hydronephrotic group of animals compared to controls on all diets, but the difference was only significant on a normal salt diet, 165 W 15 versus 86 W 12 mGU/ml respectively. In animals with severe hydronephrosis the plasma renin levels were lower, and the changes less, than in those with mild and moderate hydronephrosis. Conclusion This study demonstrates the presence of a salt-sensitive hypertension in hydronephrosis. A systemic effect of the renin–angiotensin system alone cannot be responsible for the hypertension. J Hypertens 24:1437– 1443 Q 2006 Lippincott Williams & Wilkins. Journal of Hypertension 2006, 24:1437–1443 Keywords: hydronephrosis, hypertension, nitric oxide, oxidative stress, partial ureteral obstruction, renin, salt sensitivity a Department of Medical Cell Biology, Division of Integrative Physiology, University of Uppsala, Uppsala, Sweden and b Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark Correspondence and requests for reprints to A. Erik G. Persson, Department of Medical Cell Biology, Biomedical Center, Box 571, S-75123 Uppsala, Sweden Tel: +46 18 4714180; fax: +46 18 4714938; e-mail: Erik.Persson@medcellbiol.uu.se Sponsorship: This study was financially supported by the Swedish Research Council (project no. K2003-04X-03522-32), the Wallenberg Foundation, Wallenberg consortium North, The Swedish Heart and Lung foundation (20040645) and the Ingabritt and Arne Lundberg Foundation. Received 12 January 2006 Revised 13 February 2006 Accepted 2 March 2006 Introduction Hydronephrosis due to obstruction at the level of the pelvic–ureteric junction is a fairly common condition in children, with an incidence in newborns of approximately 0.5 – 1%. The obstruction is likely to be partial, unilateral, and preferably left sided. It has been shown that the function of the hydronephrotic kidney remains surpris- ingly well preserved for several years [1,2]. This obser- vation has led to a worldwide trend towards conservative treatment of hydronephrosis. However, the long-term physiological consequences of this new policy are not known. Hypertension secondary to renal disease is found in about 5% of the hypertensive population [3]. Many different forms of renal disorder may lead to hypertension. There are a few reports on a limited number of patients with hypertension obviously caused by hydronephrosis, since the patients become normotensive after nephrectomy or pyeloplasty [4,5]. On the other hand, other investigations have shown no increase in arterial blood pressure in hydronephrosis [6]. Unilateral ureteral obstruction is a well-characterized model of renal injury [7] known to induce functional and pathological changes in the obstructed kidney [8]. In previous studies we showed that in animals with hydro- nephrosis, due to chronic unilateral partial ureteral obstruction, both renal blood flow (RBF) and glomerular filtration rate (GFR) were normal under baseline condi- tions; however, major changes occurred under volume expansion. In the hydronephrotic kidney, tubuloglomer- ular feedback (TGF), which is an important mechanism to control GFR, was reset in a paradoxical way to a much higher sensitivity and activity [9]. The same kind of TGF resetting is seen in rats of the Milan hypertensive strain (MHS) before the development of hypertension by volume retention [10]. Previously we showed that regula- tion of the TGF sensitivity is intimately coupled to nitric oxide (NO) production in the macula densa cells, since Original article 1437 These authors contributed equally to this study. 0263-6352 ß 2006 Lippincott Williams & Wilkins