Role of angiotensin II generated by angiotensin converting enzyme-independent pathways in canine kidney.
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 chymase, 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 rena1 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.
Murakami
M
M
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Matsuda
H
H
Kubota
E
E
Wakino
S
S
Honda
M
M
Hayashi
K
K
Saruta
T
T
D000804:Angiotensin II / Q000096:biosynthesis / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D007668:Kidney / Q000201:enzymology* / Q000378:metabolism; D012079:Renal Circulation / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II