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.