Heme oxygenase metabolites inhibit tubuloglomerular feedback (TGF).

American Journal of Physiology. Renal Physiology
YiLin RenOscar A Carretero

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...Continue Reading

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Citations

Jan 18, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Hong WangOscar A Carretero
Apr 18, 2012·Hypertension·Yilin RenOscar A Carretero
Jan 24, 2012·Journal of the American Society of Nephrology : JASN·Prabhleen SinghScott C Thomson
Sep 9, 2016·Physiological Reviews·Anita AyerRoland Stocker
May 8, 2013·Hypertension·Yilin RenOscar A Carretero
Sep 3, 2010·Nature Reviews. Drug Discovery·Roberto Motterlini, Leo E Otterbein
Nov 28, 2013·Current Opinion in Nephrology and Hypertension·Karl A Nath
Apr 3, 2015·Physiological Reviews·Mattias CarlströmWilliam J Arendshorst
Dec 11, 2019·Medicinal Research Reviews·Xiaoxiao YangBinghe Wang

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