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(Hypertension. 2002;39:363.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Phospholipase D Contributes to Transmural Pressure Control of Prorenin Processing in Juxtaglomerular Cell

Nobuhisa Hirota; Atsuhiro Ichihara; Yukako Koura; Matsuhiko Hayashi; Takao Saruta

From the Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

Correspondence to Takao Saruta, MD, Professor of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan, E-mail saruta{at}sc.itc.keio.ac.jp

This study was designed to delineate the involvement of phospholipase C (PLC) and phospholipase D (PLD) in transmural pressure control of renin synthesis and secretion. Primary cultures of rat juxtaglomerular (JG) cells were applied to a transmural pressure-loading apparatus for 12 hours, and the renin secretion rate (RSR), active renin content (ARC), and total (active + inactive) renin content (TRC) were determined. Under control conditions (n=5), transmural pressure decreased RSR (78.1±3.0 and 64.6±4.4% for 0 or 40 mm Hg, respectively; P<0.05) and ARC (42.8±3.3 and 26.0±3.9 ng of angiotensin I per hour per million cells for 0 or 40 mm Hg, respectively; P<0.05) but did not have a significant effect on TRC (99.5±6.7 and 89.2±4.6 ng of angiotensin I per hour per million cells for 0 or 40 mm Hg, respectively). Treatment with PLC inhibitors, 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate (200 µmol/L) and U73122 (10 µmol/L) did not alter RSR but prevented the RSR decrease with transmural pressure, whereas neither 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate nor U73122 altered ARC, TRC, or the decrease in ARC with transmural pressure. Experiments were also performed using JG cells (n=5) treated with a PLD inhibitor, 4-(2-aminoethyl)-benzensulfonyl fluoride (AEBSF, 100 µmol/L). Treatment with AEBSF did not influence basal levels of RSR, ARC, and TRC or the RSR decrease with transmural pressure. However, AEBSF did inhibit the decrease in ARC with transmural pressure. These results indicate that transmural pressure inhibits renin secretion via PLC-dependent pathways and prevents conversion of inactive renin to active renin via PLD-dependent mechanisms in JG cells.

Key Words: renin-angiotensin system • phospholipase

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