(Hypertension. 1996;27:1337-1340.)
© 1996 American Heart Association, Inc.
Articles |
Renin Regulation in Cultured Proximal Tubular Cells
From the Department of Internal Medicine, University of Texas Southwestern Medical Center, and Department of Veterans Affairs Medical Center, Dallas.
Correspondence to William L. Henrich, MD, Department of Medicine, Medical College of Ohio, PO Box 10008, Toledo, OH 43699-0008. E-mail whenrich@vortex.mco.edu.
Abstract Recent studies have documented the presence of a
complete renin-angiotensin system in the proximal
tubule of the kidney; however, little is known about the regulation of
renin in this proximal tubular system. Therefore, we performed the
present studies to learn whether the behavior of the renin system
in cultured proximal tubule is similar to that of the
juxtaglomerular renin system. Basal renin secretion
from rabbit proximal tubular cells in primary culture was low and not
affected by isoproterenol (10-5 mol/L),
diltiazem (10-5 mol/L), or a
zero-calcium bath (0 nmol/L). Only the calcium ionophore A23187
(10-4 mol/L) significantly reduced renin
secretion in these cells (from 2.44±0.37 to 1.14±0.08 ng
angiotensin I/mg protein per hour, P<.05). When
the proximal tubular cells were lysed so the effects of the test agents
on intracellular renin content could be assessed, isoproterenol caused
a significant twofold (107%) increase (from 2.02±0.56 to 4.18±0.81
ng angiotensin I/mg protein per hour, P<.05),
whereas diltiazem, A23187, and zero- and high-calcium baths did not
produce a significant change. The effects of these agents on renin mRNA
were examined in rabbit and rat proximal tubular cells in primary
culture with the use of an S1 nuclease protection assay.
Densitometry analysis of renin mRNA and either GAPDH mRNA (rat)
or 
-actin (rabbit) showed no significant alterations in renin
mRNA abundance. In summary, these results confirm the presence of renin
mRNA in cultured proximal tubular cells and suggest that a
low-level, constitutive secretion of renin occurs in this system
that is decreased by A23187. Moreover, the results also suggest that
proximal tubular renin is regulated, albeit differently from the
juxtaglomerular renin system. Finally, short-term
increments in proximal tubular renin occur without a change in renin
mRNA.
Key Words: kidney tubules, proximal • secretions • RNA, messenger • renin
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