Proximal tubular secretion of angiotensin II in rats.
It is now established that all of the components necessary for the local formation of angiotensin II (ANG II) coexist in the kidney and can alter local ANG II production rate. However, data on ANG II concentrations in different compartments within the kidney are limited. Recently, proximal tubule fluid ANG II concentrations in the nanomolar range were reported. Using an ANG II radioimmunoassay procedure with enhanced sensitivity, we performed experiments to explore proximal tubular fluid ANG II levels further and to determine the source of the ANG II. Total free-flow proximal tubular fluid samples (n = 11) had an average ANG II concentration of 13 +/- 2 nM. These concentrations were similar (10 +/- 2 nM) in samples collected into pipettes containing the inhibitors enalaprilat and EDTA (n = 17). Fluid collected from blocked proximal tubules that were perfused with artificial tubular fluid showed similar ANG II concentrations both in the presence (22 +/- 3 nM) and absence (22 +/- 4 nM) of the angiotensin-converting-enzyme inhibitor, enalaprilat, in the perfusate. Plasma ANG II concentrations were much lower and averaged 155 +/- 26 pM. Isotonic saline expansion lowered plasma ANG II levels to 30 +/- 5 pM (P < 0.01) but did not significantly decrease intraluminal ANG II (8 +/- 1 nM). These data provide further evidence that intratubular ANG II concentrations are in the nanomolar range and are regulated independently of the plasma ANG II levels. The data obtained from perfused tubules indicate that the proximal tubule adds substantial amounts of ANG II or a precursor into the tubular lumen.
Braam
B
B
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Mitchell
K D
KD
Fox
J
J
Navar
L G
LG
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D015773:Enalaprilat / Q000494:pharmacology; D007552:Isotonic Solutions; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology
D007552:Isotonic Solutions; D000804:Angiotensin II; D012965:Sodium Chloride; D004492:Edetic Acid; D015773:Enalaprilat