Ureteral Obstruction Enhances Eicosanoid Production in Cortical and Medullary Tubules of Rat Kidneys

1997 ◽  
Vol 20 (6) ◽  
pp. 398-405 ◽  
Author(s):  
Hiroyuki Yanagisawa ◽  
Kazuaki Moridaira ◽  
Makoto Nodera ◽  
Osamu Wada
1990 ◽  
Vol 37 (6) ◽  
pp. 1528-1535 ◽  
Author(s):  
Hiroyuki Yanagisawa ◽  
Jeremiah Morrissey ◽  
Aubrey R. Morrison ◽  
Saulo Klahr

1991 ◽  
Vol 261 (2) ◽  
pp. F248-F255 ◽  
Author(s):  
H. Yanagisawa ◽  
J. Morrissey ◽  
S. Klahr

Isolated glomeruli from rats with bilateral ureteral obstruction (BUO) of 24-h duration produced significantly greater amounts of prostaglandin (PG) E2 and 6-keto-PGF1 alpha in vitro than glomeruli from sham-operated control (SOC) rats. This increase was abolished by the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat, given in vivo. To elucidate the mechanisms responsible for enhanced eicosanoid production by glomeruli from rats with BUO, we measured the activities of phospholipase (PL) A2 and C and cyclooxygenase in glomeruli isolated from SOC and BUO rats. L-alpha-Phosphatidylcholine (PC)-specific and L-alpha-phosphatidylethanolamine (PE)-specific PLA2 activities were significantly greater in glomerular membranes from rats with BUO than from SOC rats. Likewise, both the activity and amount of cyclooxygenase were significantly greater in glomerular membranes of rats with BUO. Cyclooxygenase and the PE-specific PLA2 in glomerular membranes of rats with BUO remained at the levels seen in SOC rats when animals were treated in vivo before BUO with the ACE inhibitor, enalaprilat, and the thromboxane synthase inhibitor, OKY-046. Thus inhibition of vasoconstrictor formation leads to subsequent inhibition of vasodilator formation. In contrast to PE-specific PLA2, PC-specific PLA2 activities were further increased in glomerular membranes from both SOC and BUO rats pretreated with the two drugs.s The activity of phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PIP2 PLC) was significantly decreased in glomeruli from rats with BUO compared with SOC rats. We conclude that the increased synthesis of vasodilatory eicosanoids by glomeruli from rats with BUO may be mediated by enhanced activities of PE-specific PLA2 and cyclooxygenase, which are apparently stimulated by the vasoconstrictors angiotensin and thromboxane.


1985 ◽  
Vol 133 (4) ◽  
pp. 739-739
Author(s):  
B.A. Pettersson ◽  
A. Aperia ◽  
G. Elinder

Nephrology ◽  
1995 ◽  
Vol 1 (3) ◽  
pp. 191-197
Author(s):  
Hiroyuki YANAGISAWA ◽  
Nobutaka KURIHARA ◽  
Saulo KLAHR ◽  
Jerry MORRISSEY ◽  
Osamu WADA

1994 ◽  
Vol 207 (2) ◽  
pp. 234-241 ◽  
Author(s):  
H. Yanagisawa ◽  
J. Morrissey ◽  
N. Kurihara ◽  
O. Wada ◽  
S. Klahr

2000 ◽  
Vol 91 (2) ◽  
pp. 69-74 ◽  
Author(s):  
Hiroyuki Kaneto ◽  
Atsushi Fukuzaki ◽  
Shigeto Ishidoya ◽  
Atsushi Takeda ◽  
Yukihiko Ogata ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Nozomu Abe ◽  
Hiroaki Toyama ◽  
Kazutomo Saito ◽  
Yutaka Ejima ◽  
Masanori Yamauchi ◽  
...  

Background. Delayed rectifier K+-channel, Kv1.3, is most predominantly expressed in T-lymphocytes and macrophages. In such leukocytes, Kv1.3-channels play pivotal roles in the activation and proliferation of cells, promoting cellular immunity. Since leukocyte-derived cytokines stimulate fibroblasts to produce collagen fibers in inflamed kidneys, Kv1.3-channels expressed in leukocytes would contribute to the progression of tubulointerstitial renal fibrosis. Methods. Male Sprague-Dawley rats that underwent unilateral ureteral obstruction (UUO) were used at 1, 2, or 3 weeks after the operation. We examined the histological features of the kidneys and the leukocyte expression of Kv1.3-channels. We also examined the therapeutic effects of a selective channel inhibitor, margatoxin, on the progression of renal fibrosis and the proliferation of leukocytes within the cortical interstitium. Results. In rat kidneys with UUO, progression of renal fibrosis and the infiltration of leukocytes became most prominent at 3 weeks after the operation, when Kv1.3-channels were overexpressed in proliferating leukocytes. In the cortical interstitium of margatoxin-treated UUO rat kidneys, immunohistochemistry revealed reduced expression of fibrosis markers. Additionally, margatoxin significantly decreased the numbers of leukocytes and suppressed their proliferation. Conclusions. This study clearly demonstrated that the numbers of T-lymphocytes and macrophages were markedly increased in UUO rat kidneys with longer postobstructive days. The overexpression of Kv1.3-channels in leukocytes was thought to be responsible for the proliferation of these cells and the progression of renal fibrosis. This study strongly suggested the therapeutic usefulness of targeting lymphocyte Kv1.3-channels in the treatment of renal fibrosis.


Nephrology ◽  
1995 ◽  
Vol 1 (1) ◽  
pp. 31-38
Author(s):  
Hiroyuki YANAGISAWA ◽  
Jerry MORRISSEY ◽  
Nobutaka KURIHARA ◽  
Osamu WADA ◽  
Saulo KLAHR

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