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PMID: 18715939 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Heme oxygenase metabolites inhibit tubuloglomerular feedback (TGF).

American journal of physiology. Renal physiology ·Vol. 295 ·No. 4 ·2008-10-00 ·Pages F1207-12

Ren Y, D'Ambrosio MA, Wang H, Liu R, Garvin JL, Carretero OA

Abstract

Tubuloglomerular feedback (TGF) is the mechanism by which the macula densa (MD) senses increases in luminal NaCl concentration and sends a signal to constrict the afferent arteriole (Af-Art). The kidney expresses constitutively heme oxygenase-2 (HO-2) and low levels of HO-1. HOs release carbon monoxide (CO), biliverdin, and free iron. We hypothesized that renal HOs inhibit TGF via release of CO and biliverdin. Rabbit Af-Arts and attached MD were simultaneously microperfused in vitro. The TGF response was determined by measuring Af-Art diameter before and after increasing NaCl in the MD perfusate. When HO activity was inhibited by adding stannous mesoporphyrin (SnMP) to the MD perfusate, the TGF response increased from 2.1+/-0.2 to 4.1+/-0.4 microm (P=0.003, control vs. SnMP, n=7). When a CO-releasing molecule, (CORM-3; 50 microM), was added to the MD perfusate, the TGF response decreased by 41%, from 3.6+/-0.3 to 2.1+/-0.2 microm (P<0.001, control vs. CORM-3, n=12). When CORM-3 at 100 microM was added to the perfusate, it completely blocked the TGF response, from 4.2+/-0.4 to -0.2+/-0.3 microm (P<0.001, control vs. CORM-3, n=6). When biliverdin was added to the perfusate, the TGF response decreased by 79%, from 3.4+/-0.3 to 0.7+/-0.4 microm (P=0.001, control vs. biliverdin, n=6). The effects of SnMP and CORM-3 were not blocked by inhibition of nitric oxide synthase. We concluded that renal HO inhibits TGF probably via release of CO and biliverdin. HO regulation of TGF is a novel mechanism that could lead to a better understanding of the control of renal microcirculation and function.

MeSH Terms
Animals Arterioles/physiology Biliverdine/metabolism Carbon Monoxide/metabolism Feedback, Physiological/drug effects,physiology Heme Oxygenase (Decyclizing)/metabolism Heme Oxygenase-1/metabolism Kidney Glomerulus/enzymology Kidney Tubules/enzymology Male Metalloporphyrins/pharmacology Rabbits Renal Circulation/physiology
Chemicals
Metalloporphyrins stannous mesoporphyrin Carbon Monoxide Heme Oxygenase (Decyclizing) Heme Oxygenase-1 heme oxygenase-2 Biliverdine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ren YiLin
Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 Grand Blvd., Detroit, MI 48202, USA.
D'Ambrosio Martin A
Wang Hong
Liu Ruisheng
Garvin Jeffrey L
Carretero Oscar A
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Article Info
Journal
American journal of physiology. Renal physiology
Abbr.
Am J Physiol Renal Physiol
ISSN
1931-857X
DOI
10.1152/ajprenal.90243.2008
Published
2008-10-00
Epub
2008-00-20
Pages
F1207-12
Language
English
Region
United States
NLM ID
100901990
PMCID
PMC2576153
Subset
IM
Grants
NHLBI NIH HHS · HL-28982 · United States
External Links
PubMed source DOI: 10.1152/ajprenal.90243.2008 PMC Full Text View journal details
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