Arachidonic acid metabolites inhibit the stimulatory effect of angiotensin II in renal proximal tubules

Yuehong Li, Hideomi Yamada, Yoshihiro Kita, Masashi Suzuki, Yoko Endo, Shoko Horita, Osamu Yamazaki, Takao Shimizu, George Seki, Toshiro Fujita

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Abstract

Angiotensin II (Ang II) regulates renal proximal transport in a biphasic way via Ang II type 1 receptor (AT1). Whereas extracellular signal-regulated kinase (ERK) activation mediates the stimulatory effect, cytosolic phospholipase A2 (cPLA2) mediates the inhibitory effect independently of ERK. In this study, we tested the hypothesis that the cPLA2/P450 epoxygenase pathway might work to suppress the Ang II-mediated ERK activation. In the presence of arachidonic acid or 5,6-epoxyeicosatrienoic acid (EET), Ang II failed to stimulate the Na-HCO3 cotransporter activity in renal proximal tubules isolated from wild-type, AT1A-deficient, and cPLA2-α-deficient mice. In addition, Ang II failed to induce a significant ERK phosphorylation in the presence of arachidonic acid or 5,6-EET. Arachidonic acid or 5,6-EET also suppressed the stimulatory effect of Ang II on net proximal tubule bicarbonate absorption without changing cell Ca2+ concentrations. These results indicate that the cPLA2-α/P450/EET pathway blocks the stimulatory effect of Ang II by suppressing the ERK activation. Thus, the cPLA2-α/P450/EET pathway may operate as a unique negative feedback mechanism to attenuate excessive Ang II activity in the renal proximal tubules, where extremely high concentrations of Ang II are found.

Original languageEnglish
Pages (from-to)2155-2164
Number of pages10
JournalHypertension Research
Volume31
Issue number12
DOIs
Publication statusPublished - 2008 Dec 1

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ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Li, Y., Yamada, H., Kita, Y., Suzuki, M., Endo, Y., Horita, S., Yamazaki, O., Shimizu, T., Seki, G., & Fujita, T. (2008). Arachidonic acid metabolites inhibit the stimulatory effect of angiotensin II in renal proximal tubules. Hypertension Research, 31(12), 2155-2164. https://doi.org/10.1291/hypres.31.2155