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Am J Physiol Renal Physiol 287: F404-F410, 2004. First published April 20, 2004; doi:10.1152/ajprenal.00265.2003
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Angiotensin II inhibits NaCl absorption in the rat medullary thick ascending limb

Nicolas Lerolle,1,2 Soline Bourgeois,1,2 Françoise Leviel,1,3,4 Gaëtan Lebrun,1 Michel Paillard,1,3,4 and Pascal Houillier1,3,4

1Institut National de la Santé et de la Recherche Médicale U356, Institut Fédératif de Recherche 58, Universités 3René Descartes et 2Pierre et Marie Curie, and 4Département de Physiologie, Hopital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France

Submitted 25 July 2003 ; accepted in final form 12 April 2004

NaCl reabsorption in the medullary thick ascending limb of Henle (MTALH) contributes to NaCl balance and is also responsible for the creation of medullary interstitial hypertonicity. Despite the presence of angiotensin II subtype 1 (AT1) receptors in both the luminal and the basolateral plasma membranes of MTALH cells, no information is available on the effect of angiotensin II on NaCl reabsorption in MTALH and, furthermore, on angiotensin II-dependent medullary interstitial osmolality. MTALHs from male Sprague-Dawley rats were isolated and microperfused in vitro; transepithelial net chloride absorption (JCl) as well as transepithelial voltage (Vte) were measured. Luminal or peritubular 10–11 and 10–10 M angiotensin II had no effect on JCl or Vte. However, 10–8 M luminal or peritubular angiotensin II reversibly decreased both JCl and Vte. The effect of both luminal and peritubular angiotensin II was prevented by the presence of losartan (10–6 M). By contrast, PD-23319, an AT2-receptor antagonist, did not alter the inhibitory effect of 10–8 M angiotensin II. Finally, no additive effect of luminal and peritubular angiotensin II was observed. We conclude that both luminal and peritubular angiotensin II inhibit NaCl absorption in the MTALH via AT1 receptors. Because of intrarenal angiotensin II synthesis, angiotensin II concentration in medullary tubular and interstitial fluids may be similar in vivo to the concentration that displays an inhibitory effect on NaCl reabsorption under the present experimental conditions.

in vitro microperfusion; renal tubule; NaCl transport; angiotensin II subtype 1; losartan



Address for reprint requests and other correspondence: P. Houillier, Département de Physiologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France (E-mail: pascal.houillier{at}egp.ap-hop-paris.fr)




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