Tadashi Nagamatsu, Toshiyuki Nagao, Yosuke Nomura and Yoshio Suzuki
Department of Pharmacology, Faculty of Pharmacy, Meijo University, 150
Yagotoyama, Tenpaku-ku, Nagoya 468, Japan
Abstract: Immune complexes in glomeruli are involved in development
of diverse glomerulonephritis. The disposal process of glomerular immune
complexes has been unclarified. The present studies were undertaken to determine
if thromboxane A2 (TXA2) is associated with the disposal of macromolecules
in the glomeruli using mice injected with aggregated bovine serum albumin
(a-BSA). A-BSA promptly accumulated in the glomeruli, the level reaching
a plateau at 6 hr after the injection of a-BSA, and then decreased by 48
hr. The production of glomerular TXA2, prostaglandin E2 (PGE2) and prostaglandin
I2 concomitantly increased with the decrease of a-BSA in the glomeruli.
TXA2 synthase inhibitors and TXA2 receptor antagonists accelerated clearance
of glomerular a-BSA without enhancing renal tissue blood flow. They did
not affect a-BSA level in the plasma. In contrast, aminophylline, dopamine
and mannitol significantly increased renal tissue blood flow, but did not
decrease glomerular a-BSA. TXA2 synthase inhibitors decreased TXA2 production
in the glomeruli. TXA2 synthase inhibitors and TXA2 receptor antagonists
did not influence the generation of PGE2. The TXA2 analogue U-46619 significantly
increased the accumulation of a-BSA in the glomeruli. We propose that TXA2
interferes with the disposal process of aggregated protein in the glomeruli.
We also postulate that interception of glomerular activity of TXA2 may be
an effective intervention for managing immune complex-mediated glomerulonephritis
and glomerulosclerosis.
Keywords: Thromboxane A2, Prostaglandin E2, Macromolecule, Glomerulonephritis