Angiotensin II inhibits NaCl absorption in the rat medullary thick ascending limb.
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 (AT(1)) 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 (J(Cl)) as well as transepithelial voltage (V(te)) were measured. Luminal or peritubular 10(-11) and 10(-10) M angiotensin II had no effect on J(Cl) or V(te). However, 10(-8) M luminal or peritubular angiotensin II reversibly decreased both J(Cl) and V(te). The effect of both luminal and peritubular angiotensin II was prevented by the presence of losartan (10(-6) M). By contrast, PD-23319, an AT(2)-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 AT(1) 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.
Lerolle
Nicolas
N
Institut National de la Santé et de la Recherche Médicale U356, Université Pierre et Marie Curie, Paris, France.
Bourgeois
Soline
S
Leviel
Françoise
F
Lebrun
Gaëtan
G
Paillard
Michel
M
Houillier
Pascal
P
D000042:Absorption / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000378:metabolism; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012965:Sodium Chloride / Q000493:pharmacokinetics*; D013047:Specific Pathogen-Free Organisms; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000502:physiology
D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012965:Sodium Chloride