Luminal angiotensin II stimulates rat medullary thick ascending limb chloride transport in the presence of basolateral norepinephrine

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Abstract

Angiotensin II (ANG II) is secreted by the proximal tubule resulting in a luminal concentration that is 100- to 1,000-fold greater than that in the blood. Luminal ANG II has been shown to stimulate sodium transport in the proximal tubule and distal nephron. Surprisingly, luminal ANG II inhibits NaCl transport in the medullary thick ascending limb (mTAL), a nephron segment responsible for a significant amount of NaCl absorption from the glomerular ultrafiltrate. We confirmed that addition of 10−8 M ANG II to the lumen inhibited mTAL chloride transport (220 ± 19 to 165 ± 25 pmol•mm−1•min−1, P <0.01) and examined whether an interaction with basolateral norepinephrine existed to simulate the in vivo condition of an innervated tubule. We found that in the presence of a 10−6 M norepinephrine bath, luminal ANG II stimulated mTAL chloride transport from 298 ± 18 to 364 ± 42 pmol•mm−1•min−1 (P <0.05). Stimulation of chloride transport by luminal ANG II was also observed with 10−3 M bath dibutyryl cAMP in the bathing solution and bath isoproterenol. A bath of 10−5 H-89 blocked the stimulation of chloride transport by norepinephrine and prevented the effect of luminal ANG II to either stimulate or inhibit chloride transport. Bath phentolamine, an α-adrenergic agonist, also prevented the decrease in mTAL chloride transport by luminal ANG II. Thus luminal ANG II increases chloride transport with basolateral norepinephrine; an effect likely mediated by stimulation of cAMP. Alpha-1 adrenergic stimulation prevents the inhibition of chloride transport by luminal ANG II.

Original languageEnglish (US)
Pages (from-to)F294-F299
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number4
DOIs
StatePublished - Feb 15 2016

Keywords

  • Chloride transport
  • Hormonal interaction
  • Microperfusion
  • NKCC2
  • Norepinephrine

ASJC Scopus subject areas

  • Physiology
  • Urology

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