Role of protein kinase C in angiotensin II-induced constriction of renal microvessels

Takahiko Nagahama, Koichi Hayashi, Yuri Ozawa, Tsuneo Takenaka, Takao Saruta

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Background. Although angiotensin II (Ang II) exerts its action through multiple vasomotor mechanisms, the contribution of phosphoinositol hydrolysis products to Ang II-induced renal vasoconstriction remains undetermined. Methods. The role of protein kinase C (PKC) in Ang II-induced afferent (AFF) and efferent (EFF) arteriolar constriction was examined using the isolated perfused hydronephrotic rat kidney. Results. Ang II (0.3 nmol/L)-induced EFF constriction was refractory to inhibition of voltage-dependent calcium channels by pranidipine (1 μmol/L, 19 ± 2% reversal) but was completely reversed by a PKC inhibitor, chelerythrine (1 μmol/L, 96 ± 2% reversal). Furthermore, direct PKC activation by phorbol myristate acetate (PMA; 1 μmol/L) caused prominent EFF constriction, and this constriction was inhibited by manganese and free calcium medium. In contrast, Ang II-induced AFF constriction was completely abolished by pranidipine (98 ± 4% reversal) and was partially inhibited by chelerythrine (55 ± 3% reversal). Although PMA elicited marked AFF constriction, this constriction was insensitive to the calcium antagonist, but was totally inhibited by manganese or free calcium medium conclusions. PKC plays an obligatory role in Ang II-induced EFF constriction that requires extracellular calcium entry through nonselective cation channels. In contrast, in concert with our recent findings demonstrating a complete dilation by thapsigargin, Ang II-induced AFF constriction is mainly mediated by inositol trisphosphate (IP3) and voltage-dependent calcium channel pathways, but could not be attributed to the PKC-activated calcium entry pathway (for example, nonselective cation channels). Rather, Ang II-stimulated PKC may cross-talk to the IP3/voltage- dependent calcium channel pathway and could modulate the vasoconstrictor mechanism of the AFF. Thus, the role of PKC during Ang II stimulation differs in AFF and EFF, which may constitute segmental heterogeneity in the renal microvasculature.

Original languageEnglish
Pages (from-to)215-223
Number of pages9
JournalKidney international
Volume57
Issue number1
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • Afferent arterioles
  • Cation channels
  • Efferent arterioles
  • Renal microvasculature
  • Vasoconstriction
  • Voltage- dependent Ca channels

ASJC Scopus subject areas

  • Nephrology

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