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

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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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
JournalKidney International, Supplement
Volume51
Issue number63
Publication statusPublished - 1997

Fingerprint

Peptidyl-Dipeptidase A
Angiotensin II
Canidae
Kidney
Angiotensin I
Renal Circulation
Vasoconstriction
Constriction
Arterial Pressure
Angiotensin Receptors
Enzyme Assays
Arterioles
Needle Biopsy
Renal Artery
Renin-Angiotensin System
Needles
Hemodynamics
High Pressure Liquid Chromatography
Peptides

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Role of angiotensin II generated by angiotensin converting enzyme- independent pathways in canine kidney. / Murakami, M.; Matsuda, H.; Kubota, E.; Wakino, Shu; Honda, M.; Hayashi, K.; Saruta, T.

In: Kidney International, Supplement, Vol. 51, No. 63, 1997.

Research output: Contribution to journalArticle

Murakami, M. ; Matsuda, H. ; Kubota, E. ; Wakino, Shu ; Honda, M. ; Hayashi, K. ; Saruta, T. / Role of angiotensin II generated by angiotensin converting enzyme- independent pathways in canine kidney. In: Kidney International, Supplement. 1997 ; Vol. 51, No. 63.
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