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May 1, 1993AJP Renal Physiology238 citations

Proximal tubular secretion of angiotensin II in rats

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BBBranko BraamHeart Failure & TransplantKMKenneth D. MitchellBio-Rad (United States)JFJohn FoxTulane University

Key Result

Isotonic saline expansion in rats lowered plasma ANG II levels to 30 pM (P<0.01) but did not significantly decrease intraluminal ANG II, indicating independent regulation.

Structured PICO

P
Population
Rats (preclinical model)
I
Intervention
Measurement of proximal tubular fluid angiotensin II (ANG II) concentrations using radioimmunoassay, including perfusion with artificial tubular fluid and isotonic saline expansion
C
Comparator
Plasma ANG II concentrations; presence vs absence of enalaprilat
O
Outcome
Angiotensin II concentrations in proximal tubular fluid and plasmasurrogate

The proximal tubule secretes substantial amounts of angiotensin II into the tubular lumen, maintaining nanomolar concentrations that are regulated independently of plasma levels.

Main Result

Absolute Event Rate: 30% vs 155%

p-value: p=< 0.01

Abstract

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.

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Cite This Study

Braam et al. (1993) studied this question. Isotonic saline expansion vs. Baseline was evaluated on Plasma ANG II levels (pM) (p=< 0.01). Isotonic saline expansion in rats lowered plasma ANG II levels to 30 pM (P<0.01) but did not significantly decrease intraluminal ANG II, indicating independent regulation.

synapsesocial.com/papers/6a6d3d615d37378ac1db7f2dhttps://doi.org/10.1152/ajprenal.1993.264.5.f891
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