Tubular fluid concentrations and kidney contents of angiotensins I and II in anesthetized rats

Abstract

Previous micropuncture studies have reported nanomolar concentrations of angiotensin II in proximal tubular fluid and have indicated that angiotensin II or a precursor may be secreted into the tubular lumen. Further experiments were performed to determine if proximal tubular fluid angiotensin I concentrations are also greater than plasma and kidney levels and to estimate the degree of intrarenal compartmentalization of the angiotensin peptides. Free-flow proximal tubular fluid samples were collected in micropipets and were pooled for each animal. At the end of each experiment, a blood sample was collected and the micropunctured left kidney was harvested and homogenized in methanol. The angiotensin I concentration in proximal tubular fluid samples averaged 6.1 ± 1.2 pmol/mL, whereas the angiotensin II concentration averaged 8.1 ± 1.6 pmol/mL (N = 13). HPLC analysis of a separate sample pooled from collections in five rats indicated that the immunoreactive angiotensin I and angiotensin II primarily represented authentic angiotensin I and II. Plasma concentrations of angiotensin I and angiotensin II averaged 0.39 ± 0.09 and 0.15 ± 0.03 pmol/mL, respectively. The kidney contents of angiotensin I and angiotensin II were 1.28 ± 0.24 and 0.97 ± 0.17 pmol/g of kidney, respectively. These findings indicate that proximal tubular fluid contains nanomolar concentrations of angiotensin I as well as angiotensin II. These high tubular fluid concentrations, which greatly exceed the plasma and kidney levels, likely reflect net secretion of the angiotensin peptides by proximal tubule cells. Comparison of the tissue levels of angiotensin I and angiotensin II, measured in the same kidneys subjected to micropuncture procedures, with the proximal tubular fluid samples suggests substantive intrarenal compartmentalization of approximately 10 to 20%.