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Possible mediators of connecting tubule glomerular feedback.

Hypertension (Dallas, Tex. : 1979) (2008-12-03)
YiLin Ren, Martin A D'Ambrosio, Jeffrey L Garvin, Hong Wang, Oscar A Carretero
ZUSAMMENFASSUNG

In the renal cortex, the connecting tubule (CNT) returns to the glomerular hilum and contacts the afferent arteriole (Af-Art). Increasing Na delivery to the CNT dilates the Af-Art by activating epithelial Na channels, a process that we call connecting tubule glomerular feedback (CTGF). However, the mediator(s) of CTGF are unknown. We tested the hypothesis that Na reabsorption by the CNT induces release of arachidonic acid metabolites that diffuse to and dilate the Af-Art. Microdissected rabbit Af-Arts and adherent CNTs were simultaneously microperfused. CTGF was measured as the increase in diameter of norepinephrine-preconstricted Af-Arts in response to switching NaCl concentration in the lumen of the CNT from 10 to 80 mmol/L. Under control conditions, CTGF was repeatable and completely reversed norepinephrine-induced vasoconstriction. In the presence of 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, CTGF was completely blocked (-0.7+/-0.3 versus 7.3+/-0.5 microm), suggesting that arachidonic acid metabolites mediate CTGF. Because both cyclooxygenase-derived prostaglandins and epoxygenase-derived epoxyeicosatrienoic acids are known vasodilatory arachidonic acid metabolites, we tested whether indomethacin or MS-PPOH (a cyclooxygenase and an epoxygenase inhibitor) could block CTGF. Both indomethacin and MS-PPOH partially blocked CTGF (2.3+/-0.8 versus 6.5+/-0.5 microm, and 2.9+/-0.8 versus 6.6+/-1.1 microm, respectively). When combined, they completely blocked CTGF (-0.4+/-0.3 versus 6.6+/-1.1 microm). We confirmed these findings by using the epoxyeicosatrienoic acid antagonist 14,15-EEZE. The combination of indomethacin plus 14,15-EEZE completely abolished CTGF (-0.3+/-0.2 versus 8.0+/-1.0 microm). We conclude that increasing Na concentrations in the CNT stimulate release of prostaglandins and epoxyeicosatrienoic acids, which mediate CTGF.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
5,8,11,14-Eicosatetraynsäure, ≥97%