Effects of Ureteral Obstruction on Eicosanoid Production by Isolated Glomeruli

Author(s):  
Hiroyuki Yanagisawa ◽  
Jeremiah J. Morrissey ◽  
Saulo Klahr
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.


1990 ◽  
Vol 258 (1) ◽  
pp. F85-F93 ◽  
Author(s):  
H. Yanagisawa ◽  
J. Morrissey ◽  
A. R. Morrison ◽  
M. L. Purkerson ◽  
S. Klahr

The production of prostaglandin (PG) E2, 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) under basal conditions and after exposure to angiotensin II (ANG II) or arginine vasopressin (AVP) was examined in vitro in isolated glomeruli. The glomeruli were obtained from control rats and rats with bilateral ureteral obstruction (BUO) of 24-h duration that were pretreated or not with an inhibitor of the angiotensin I converting enzyme (ACE). Basal prostanoid production was greater in isolated glomeruli from BUO rats than in controls. Administration of an ACE inhibitor, enalaprilat, given in vivo returned basal prostanoid production by isolated glomeruli of BUO rats to levels seen in glomeruli of control rats. The prostanoid production in response to addition of ANG II or AVP in vitro was blunted in glomeruli from BUO rats, but the response was restored to “normal” after blockade of ANG II synthesis in vivo in BUO rats. Blockade of ANG II synthesis in vivo did not affect prostanoid synthesis by isolated glomeruli of control rats. The prostanoid generation in response to addition of both ANG II and arachidonic acid in vitro compared with ANG II addition alone was not significantly stimulated in glomeruli from BUO rats. In contrast, it was significantly stimulated in glomeruli of control rats. The results indicate that endogenous ANG II has an important role in the increased synthesis of prostanoids found in isolated glomeruli of rats with BUO and that the in vitro prostanoid production in response to ANG II and AVP can be restored to normal when the synthesis of ANG II is inhibited in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)


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

1997 ◽  
Vol 20 (6) ◽  
pp. 398-405 ◽  
Author(s):  
Hiroyuki Yanagisawa ◽  
Kazuaki Moridaira ◽  
Makoto Nodera ◽  
Osamu Wada

1988 ◽  
Vol 254 (6) ◽  
pp. E687-E693
Author(s):  
G. P. Brown ◽  
R. C. Venuto

The low renal resistance to blood flow in the presence of an activated endogenous renin-angiotensin system in gravid animals may in part be mediated by the action of eicosanoids produced in situ. To evaluate intrarenal eicosanoid production during gestation in rabbits, we quantitated immunoreactive PGE2, 6-keto-PGF1 alpha (a stable metabolite of PGI2) and thromboxane B2 (a stable metabolite of thromboxane A2) in unextracted media after incubation of renal slices and isolated glomeruli. In cortical slices from nonpregnant and pregnant rabbits, PGE2 production (micrograms.g-1.30 min-1) was 0.04 +/- 0.005 and 0.08 +/- 0.01 (P less than 0.01) and 6 keto-PGF1 alpha was 0.03 +/- 0.01 and 0.06 +/- 0.01 (P less than 0.05), respectively. In papillary slices, PGE2 production was 14 +/- 2 and 21 +/- 2 (P less than 0.05) and 6 keto-PGF1 alpha was 4 +/- 1 and 5 +/- 1 (P greater than 0.05) for nonpregnant and pregnant rabbits, respectively. Thromboxane B2 production was unchanged during pregnancy in both cortex and papilla. Acute captopril administration to nonpregnant and to pregnant rabbits in vivo failed to alter in vitro renal slice eicosanoid production. Isolated glomeruli from nonpregnant and pregnant rabbits synthesized PGE2 at similar rates. Exogenous arachidonic acid increased PGE2 production (P less than 0.05), but angiotensin II had no effect on eicosanoid production in vitro. These data suggest that the net synthesis of vasodilator eicosanoids is enhanced during gestation in rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)


1994 ◽  
Vol 46 (1) ◽  
pp. 245-251 ◽  
Author(s):  
Hiroyuki Yanagisawa ◽  
Nobutaka Kurihara ◽  
Saulo Klahr ◽  
Jerry Morrissey ◽  
Osamu Wada

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