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Effect of basolateral CO 2 on the luminal ANG II sensitivity of HCO 3 reabsorption by rabbit S2 proximal tubules
Author(s) -
Zhou Yuehan,
Boron Walter F
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.760.2
Subject(s) - reabsorption , chemistry , medicine , endocrinology , angiotensin ii , nephron , receptor , kidney , biology , biochemistry
Our previous work showed that: (1) Using out‐of‐equilibrium (OOE) solutions to raise basolateral (BL) [CO 2 ] from 0% to 20% causes graded increases of HCO 3 reabsorption ( J HCO3 ) by the proximal tubule (PT). (2) Adding ANG II to the lumen (L) produces dose‐dependent effects on J HCO3 . (3) Blockade or knockout of the apical AT 1A receptor prevents the response to BL CO 2 , consistent with the observation of others that the PT secretes an ANG II‐related product into the lumen. And (4) BL but not L lisinopril (apparently by blocking intracellular ACE activity) prevents the action of BL CO 2 , suggesting that the PT secretes preformed ANG II. To obtain a “true” dose‐response curve for the effect of L ANG II on CO 2 ‐evoked HCO 3 reabsorption, we blocked secretion of preformed ANG II by exposing isolated perfused PTs to 240 nM BL lisinopril. Adding 10 −11 M exogenous ANG II to L increased J HCO3 by 43% at [CO 2 ] BL = 5% (P = 0.01, n = 5) and by 61% at [CO 2 ] BL = 20% (P = 0.02, n = 5), but had no effect at [CO 2 ] BL = 0% (P = 0.37, n = 6). Further, adding 10 −9 M ANG II to L raised J HCO3 by 60% at [CO 2 ] BL = 20% (P = 0.01, n = 6) but had no effect at [CO 2 ] BL = 5% (P = 0.33, n = 5). Our data indicate that the PT's ability to raise J HCO3 in response to increases in [ANG II] L absolutely requires basolateral CO 2 , and that the response rises with increases in [CO 2 ] BL . Thus, CO 2 plays an important role in the signal‐transduction pathway initiated by luminal ANG II.