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Am J Physiol Renal Physiol (April 20, 2004). doi:10.1152/ajprenal.00265.2003
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Submitted on July 25, 2003
Accepted on April 12, 2004

Angiotensin II inhibits NaCl absorption in the rat medullary thick ascending limb

Nicolas Lerolle1, Soline Bourgeois1, Francoise Leviel1, Gaetan Lebrun1, Michel Paillard1, and Pascal Houillier1*

1 INSERM Unite 356, Institut Federatif de Recherche 58, Paris, France; Department of Physiology, Universite Rene Descartes et Pierre et Marie Curie, Paris, France; Department of Physiology, Hopital Europeen Georges Pompidou, Paris, France

* To whom correspondence should be addressed. E-mail: pascal.houillier{at}egp.ap-hop-paris.fr.

NaCl reabsorption in the medullary thick ascending limb of Henle (MTALH) contributes to NaCl balance and is, also, responsible for the creation of the medullary interstitial hypertonicity. Despite the presence of AT1 receptors in both the luminal and the basolateral plasma membranes of the MTALH cells, no information is available on the effect of angiotensin II on NaCl reabsorption in MTALH and, further, on the angiotensin II-dependent medullary interstitial osmolality. MTALH 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, PD123319, 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.




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