Colocalization and release of angiotensin and renin in renal cortical cells.
Angiotensin is generated within the kidney, but the precise loci for the formation of angiotensin I (ANG I) and angiotensin II (ANG II) have not been demonstrated. We performed electron microscopy immunocytochemistry in kidney sections of 10-day-old (newborn) and adult Wistar-Kyoto (WKY) rats using specific antibodies to renin, ANG I, ANG II, and angiotensinogen (AO). Renin, ANG I, ANG II, and AO were present in juxtaglomerular (JG) cells. Renin was largely confined to cytoplasmic granules; ANG I and ANG II were colocalized to these granules but also were present in the cytoplasm; AO was distributed throughout the cytoplasm. AO also was present in a renal cortical distribution in proximal tubular cells. Northern blot analysis demonstrated AO mRNA in total kidney and liver but not in renal microvessels. Using the reverse hemolytic plaque assay, we demonstrated release of ANG I and renin from individual renocortical cells of adult WKY rats. Under control conditions, the number of releasing cells was 11 +/- 1 for ANG I and 10 +/- 1 for renin. Addition of rat renin inhibitor (RI) (1 x 10(-5) M), which inhibited renin activity in the medium from 37 to 9 pg ANG I.ml-1.h-1, did not alter ANG I plaque number. Addition of rat AO increased ANG I plaque number to 17 +/- 2 (P less than 0.05). Incubation with both RI and AO prevented the increase in ANG I plaque number obtained with AO alone. Enalapril treatment (7 days; n = 5) increased the number of plaque-forming cells to 22 +/- 2 for ANG I (P less than 0.0005) and to 39 +/- 7 for renin (P less than 0.001). The results suggest an intracellular location for AO and angiotensin and release of renin and ANG I by renal cortical cells and suggest that released angiotensin is produced intracellularly and that secretion of ANG I is augmented by converting enzyme inhibition.
Hunt
M K
MK
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Ramos
S P
SP
Geary
K M
KM
Norling
L L
LL
Peach
M J
MJ
Gomez
R A
RA
Carey
R M
RM
D000803:Angiotensin I / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism*; D000808:Angiotensinogen / Q000378:metabolism; D000818:Animals; D004656:Enalapril / Q000494:pharmacology; D006462:Hemolytic Plaque Technique; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D051381:Rats; D011921:Rats, Inbred WKY; D012083:Renin / Q000378:metabolism*; D014018:Tissue Distribution; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D000808:Angiotensinogen; D004656:Enalapril; D012083:Renin; D000092502:Renin Inhibitors