title: Possible mechanism of efferent arteriole (Ef-Art) tubuloglomerular feedback.
abstract: Adenosine triphosphate (ATP) is liberated from macula densa cells in response to increased tubular NaCl delivery. However, it is not known whether ATP from the macula densa is broken down to adenosine, or whether this adenosine mediates efferent arteriole (Ef-Art) tubuloglomerular feedback (TGF). We hypothesized that increased macula densa Ca(2+), release of ATP and degradation of ATP to adenosine are necessary for Ef-Art TGF. Rabbit Ef-Arts and adherent tubular segments (with the macula densa) were simultaneously microperfused in vitro while changing the NaCl concentration at the macula densa. The Ef-Art was perfused orthograde through the end of the afferent arteriole (Af-Art). In Ef-Arts preconstricted with norepinephrine (NE), increasing NaCl concentration from 10 to 80 mM at the macula densa dilated Ef-Arts from 7.5+/-0.7 to 11.1+/-0.3 microm. Buffering increases in macula densa Ca(2+) with the cell-permeant Ca(2+) chelator BAPTA-AM diminished Ef-Art TGF from 3.1+/-0.3 to 0.1+/-0.2 microm. Blocking adenosine formation by adding alpha-beta-methyleneadenosine 5'-diphosphate (MADP) blocked Ef-Art TGF from 2.9+/-0.5 to 0.1+/-0.2 microm. Increasing luminal NaCl at the macula densa from 10 to 45 mM caused a moderate Ef-Art TGF response, 1.3+/-0.1 microm. It was potentiated to 4.0+/-0.3 microm by adding hexokinase, which enhances conversion of ATP into adenosine. Our data show that in vitro changes in macula densa Ca(2+) and ATP release are necessary for Ef-Art TGF. ATP is broken down to form adenosine, which mediates signal transmission of Ef-Art TGF.
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Michigan 48202, USA. yren1@hfhs.org
authors.forename: Y
authors.initials: Y
authors.lastname: Ren
authors.forename: J L
authors.initials: JL
authors.lastname: Garvin
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.forename: O A
authors.initials: OA
authors.lastname: Carretero
mesh_terms: D000241:Adenosine / Q000502:physiology; D000818:Animals; D001160:Arterioles / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005246:Feedback; D007606:Juxtaglomerular Apparatus / Q000187:drug effects / Q000502:physiology*; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D011817:Rabbits; D015291:Transforming Growth Factors / Q000502:physiology
chemical_list: C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D015291:Transforming Growth Factors; D000241:Adenosine