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Carbon monoxide inhibits tubuloglomerular feedback in vivo by activation of soluble guanylyl cyclase
Author(s) -
Wang Hong,
Garvin Jeffrey L.,
Carretero Oscar A.
Publication year - 2010
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.24.1_supplement.984.12
Subject(s) - chemistry , soluble guanylyl cyclase , tubuloglomerular feedback , in vivo , cyclic guanosine monophosphate , medicine , endocrinology , nitric oxide , guanosine , guanylate cyclase , renal function , biochemistry , biology , microbiology and biotechnology , organic chemistry
We have previously shown in vitro that carbon monoxide (CO) inhibits tubuloglomerular feedback (TGF), but how this happens is not known. We hypothesized that CO in vivo inhibits TGF by activating the soluble guanylyl cyclase (sGC)/cyclic guanosine 3′, 5′‐monophosphate (cGMP) system. Renal micropuncture studies were performed in male Sprague Dawley rats. TGF was induced by increasing late proximal perfusion rate (0, 10, 20, 30, 40 nL/min) while measuring stop‐flow pressure (P SF ) as an index of single nephron glomerular filtration. We measured the effect of a CO‐donor, CORM‐3 (50 μM) on P SF max with and without inhibition of sGC using the sGC inhibitor LY83583 (1 μM). First, we demonstrated that the P SF response to increased tubular perfusion rate was reversible and reproducible. Next, we found CORM‐3 blunted the TGF response, as the maximum change in P SF was 6.9 ± 0.2 mmHg in controls, but only 3.9 ± 0.4 mmHg in CORM‐3 treated tubules ( p < 0.001). However, with addition of LY83583 to the perfusate, the effect of CORM‐3 was eliminated. Addition of LY83583 potentiated the TGF response by 28% (8.4 ± 0.3 mmHg, p < 0.001), and it also reversed the blunting effect of CORM‐3 (8.3 ± 0.4 mmHg, p < 0.001) to a similar extent. From these data, we conclude that inhibition of TGF by CO in vivo is mediated by activation of the sGC/cGMP system. This study was supported by National Institutes of Health Grant HL‐090550.