Role of angiotensin II generated by angiotensin converting enzyme- independent pathways in canine kidney

M. Murakami, H. Matsuda, E. Kubota, S. Wakino, M. Honda, K. Hayashi, T. Saruta

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Abstract

Recent studies have provided evidence of angiotensin converting enzyme (ACE)-independent angiotensin (Ang) II formation in tissue renin-angiotensin systems. We studied the effects of Ang II generated by ACE-independent pathways on renal hemodynamics. We used a synthetic peptide, [Pro11, D- Ala12]-Ang I (S), which yields Ang II by chymasa, but not by ACE. Infusion of Ang I into a renal artery caused a decrease in renal blood flow, and reciprocally an increase in mean arterial pressure. Infusion of S (1 nmol/kg) caused a decrease in renal blood flow (-20%), but a larger dose was needed to increase mean arterial pressure. Studies with an intravital needle-probe CCD camera revealed that the Ang I infusion induced dose-dependent vasoconstriction of afferent and efferent arterioles (49% and 54%, respectively at 1 nmol/kg). In contrast, infusion of S elicited only 30% constriction of these vessels at a dose of 1 nmol/kg and induced no further constriction at higher doses, indicating that different segments of renal vessels responded in different fashions to Ang II formed via ACE-independent pathways. These vasoconstrictions were abolished by an angiotensin II receptor (AT-1) antagonist. Enzymatic assays using reverse-phase HPLC revealed that the ACE-dependent pathway was predominant in the renal cortex (approximately 80%). We also determined Ang II concentrations in renal cortex specimens obtained by needle biopsy. Intrarenal S infusion (10 nmol/kg) increased plasma and renal Ang II concentrations to 160% and 710% of the respective baseline levels. This study provides in vivo evidence of ACE- independent Ang II formation in renal tissue and suggests that this locally- formed Ang II influences the renal circulation in a paracrine fashion.

Original languageEnglish
Pages (from-to)S132-S135
JournalKidney International, Supplement
Volume51
Issue number63
Publication statusPublished - 1997 Dec 1

Keywords

  • Angiotensin II
  • Angiotensin converting enzyme
  • Chymase
  • Hemodynamics
  • Kidney

ASJC Scopus subject areas

  • Nephrology

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    Murakami, M., Matsuda, H., Kubota, E., Wakino, S., Honda, M., Hayashi, K., & Saruta, T. (1997). Role of angiotensin II generated by angiotensin converting enzyme- independent pathways in canine kidney. Kidney International, Supplement, 51(63), S132-S135.