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S Klahr

Publications and source records attributed to S Klahr.

At least 19 recordsLinked to original sources
PubMed1992

Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy.

We studied the effect of dietary supplementation with L-arginine for 6 weeks on the progression of renal disease in female Sprague-Dawley rats subjected to sham-operation (groups 1 and 2) or surgical ablation of 85% to 90% of the total renal mass (groups 3 and 4). All rats were fed a standard rat chow containing 22.8% protein. Rats in groups 1 (n = 5) and 3 (n = 9) served as controls and drank tap water ad libitum. Rats in groups 2 (n = 6) and 4 (n = 6) drank tap water supplemented with 1% L-arginine. Rats in groups 1 and 2 had similar values for glomerular and tubular function and serum chemistries 6 weeks after sham-operation. Sham-operated rats given L-arginine had significantly greater urine urea excretion than similar rats drinking tap water. Rats with subtotal nephrectomy (groups 3 and 4) had a significantly higher blood pressure, greater proteinuria, and a significantly lower plasma albumin than sham-operated rats (groups 1 and 2). Rats with remnant kidneys given 1% L-arginine (group 4) had significantly greater values for glomerular filtration rate (GFR) and P-amino hippurate (PAH) clearance than similar rats given tap water (group 3), despite comparable levels of systemic blood pressure, hematocrit, body weight, plasma chemistries, including L-arginine, and urine chemistries, except urea excretion. The remnant kidney of rats given L-arginine (group 4) had a greater number of normal or minimally abnormal glomeruli and fewer interstitial changes than that of rats given tap water (group 3).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Role of the 5-lipooxygenase pathway in obstructive nephropathy.

Leukotrienes are products of the 5-lipooxygenase pathway of arachidonic acid metabolism that possess potent inflammatory properties. We examined the potential role of this pathway in the decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) observed in rats after unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Isolated glomeruli from rats with BUO produced significantly greater amounts of leukotriene B4 (LTB4) than glomeruli from sham-operated rats (SOR; P less than 0.0001). Glomeruli from rats with BUO given MK886, an inhibitor of the 5-lipooxygenase enzyme, or from rats with BUO subjected to both total body irradiation to prevent the leukocyte infiltration of the kidney and also given MK886 prior to obstruction, produced amounts of LTB4 not significantly different from those in glomeruli of SOR. Glomeruli from rats with BUO that had only total body irradiation prior to obstruction produced significantly less LTB4 than glomeruli from untreated BUO rats, but LTB4 production was still significantly greater than in glomeruli from SOR. There were no significant differences in GFR among SOR, SOR given MK886, and SOR subjected to total body irradiation. However, SOR given MK886 had significantly higher ERPF and lower renal vascular resistance (RVR) than SOR not pretreated with the lipooxygenase inhibitor. Rats with BUO given MK886, or subjected to total body irradiation, or both, prior to obstruction had significantly greater GFR and ERPF values and lower RVR than untreated BUO rats. Glomeruli from rats with BUO which were not pretreated had three times the leukocytes of glomeruli from SOR. This leukocyte infiltrate was composed of macrophages (about 55%) and neutrophils (about 45%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Protein increases glomerular eicosanoid production and activity of related enzymes.

We examined the in vitro production of PGE2, 6-keto PGF1 alpha and TxB2 by isolated glomeruli from rats fed a low (6% casein) or a high (40% casein) protein diet for approximately eight weeks. Glomeruli from high protein-fed rats produced significantly greater amounts of PGE2, 6-keto PGF1 alpha and TxB2 under basal conditions and in response to the addition of 100 nM angiotensin II (Ang II) than glomeruli from low protein-fed rats. To elucidate the mechanisms by which greater protein intake enhanced the glomerular production of eicosanoids, we explored phospholipase (A2 and C) and cyclooxygenase activity in glomeruli isolated from low- or high-protein fed rats. PE-specific PLA2 activities were significantly increased in glomeruli from rats fed a high protein diet when compared to a low protein diet. On the other hand, PC-specific PLA2 activities were significantly decreased in glomeruli from rats fed a high protein diet. No significant difference in PIP2-PLC activities was detected between glomeruli of the two dietary groups. The cyclooxygenase content and activity was significantly greater in glomeruli from rats fed a high protein diet than in glomeruli from rats fed a low protein diet. Glomeruli of rats fed a 50/50 mixture of the diets (23% casein) had amounts and activity of cyclooxygenase and activities of PE-specific PLA2 intermediate between those of high and low protein-fed animals. In conclusion, increased synthesis of eicosanoids by glomeruli from rats fed a high protein diet may be mediated by increases in the amount and activity of cyclooxygenase coupled with enhanced activity of PE-specific PLA2.

Angiotensin II↗
PubMed1992

G-protein stimulation inhibits amiloride-sensitive Na/H exchange independently of cyclic AMP.

G-proteins are heterotrimeric proteins involved in many transmembrane signaling events. Both the renal basolateral membrane and the renal brush border membrane contain large quantities of these proteins. G-proteins appear related to hormonal signaling in the basolateral membrane and presumably affect ion gating in the brush border. We investigated the influence of G-proteins on the amiloride-sensitive Na/H exchanger, the activity of which is regulated at least in part by cAMP-dependent protein kinase, by measuring the amiloride-sensitive component of [22Na+] uptake in rat renal brush border membrane vesicles (BBMV) in the presence of a pH gradient. Incubation of vesicles with AlF4- (10 microM Al3+, 10 mM F-) resulted in significant inhibition of amiloride-sensitive [22Na+] uptake at both 20 seconds and 5 minutes of incubation. Incorporation of GTP gamma S into BBMV by transient hypotonic lysis also resulted in significantly reduced amiloride-sensitive [22Na+] uptake compared to controls at both time points. This inhibition could be reversed by GDP beta S. Similar lysis in the presence of 10 microM GDP beta S alone had no significant effect. When Na(+)-dependent [14C]-D-glucose uptake into BBMV was studied no significant effect of these G-protein modulating agents was observed. Adenylate cyclase activity could not be stimulated in these BBMV preparations using standard techniques. Furthermore, cAMP-dependent protein kinase activity, strongly stimulated in these BBMV by exogenously added cAMP, was not stimulated by 10 microM GTP gamma S alone. These findings suggest that the amiloride-sensitive Na/H exchanger can be regulated by G-proteins independently of adenylate cyclase and cAMP-dependent protein kinase.

Adenylyl Cyclases↗
PubMed1992

Renal function after release of ureteral obstruction: role of endothelin and the renal artery endothelium.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) are decreased and mean arterial pressure (MAP) is increased after unilateral release of bilateral ureteral obstruction (BUO). An imbalance between vasoconstrictor and vasodilator substances may explain the hemodynamic alterations seen in this setting. The present study examines the role of endothelin-1 in such alterations. Rats with BUO (N = 10) had significantly lower GFR and ERPF (ml/min/kg body wt) than sham-operated rats (SOR, N = 9) (1.40 +/- 0.14 vs. 6.20 +/- 0.38 and 5.12 +/- 0.68 vs. 20.2 +/- 2.20, respectively) and significantly higher MAP (mm Hg) than SOR (154.9 +/- 3.2 vs. 120.6 +/- 1.7). Rats with BUO given a specific antiendothelin antibody (N = 8) had significantly higher GFR (2.10 +/- 0.12) and ERPF (7.46 +/- 0.95) than BUO control rats, but there were no significant changes in MAP (159.5 +/- 5.8). In SOR (N = 6), mechanical denudation of the main renal artery endothelium did not significantly affect renal function when compared to renal function in control SOR. However, the same maneuver significantly lowered GFR (0.64 +/- 0.17) and ERPF (1.67 +/- 0.36) in BUO rats (N = 5) when compared to BUO control rats. We conclude that: (1) endothelin-1 has a significant vasoconstrictor role in rats with BUO of 24 hours duration and accounts for a portion of the decrease in glomerular filtration rate seen in rats after unilateral release of bilateral ureteral obstruction, and (2) in the BUO setting, the net role of the renal artery endothelium is vasodilatory.

Animals↗
PubMed1992

EDRF role in renal function and blood pressure of normal rats and rats with obstructive uropathy.

There is a decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) and an increase in mean arterial pressure (MAP) and renal vascular resistance (RVR) after release of bilateral ureteral obstruction (BUO) of 24 hours duration. The present studies examine the role of endothelium-derived relaxing factor (EDRF) in the renal hemodynamics of sham-operated rats (SOR) and rats in which BUO of 24 hours duration was unilaterally released. In both groups of rats, renal function and blood pressure were measured in the awake state under basal conditions and after administration of L-arginine (L-arg), the substrate for EDRF synthesis, followed by NwNAME, an L-arg antagonist, or after administration of NwNAME followed by L-arg. Administration of L-arg alone to SOR did not affect renal function, MAP or RVR. In SOR given L-arg and then NwNAME, there was significantly decreased GFR and ERPF and increased MAP and RVR. When NwNAME was given initially, similar changes were obtained, and these were reversed by the administration of L-arg. Rats given L-arginine immediately after unilateral release of BUO of 24 hours duration had significantly greater GFR and ERPF values and lower MAP and RVR than temporal controls. NwNAME given to BUO rats decreased renal function further and increased MAP and RVR. We found a dose-dependent increase in GFR and ERPF and a dose-dependent decrease in MAP and RVR in both SOR and rats with BUO given increasing amounts of L-arg. There was also a dose-dependent decrease in GFR and ERPF and an increase in MAP and RVR in SOR and rats with BUO given increasing amounts of NwNAME or NGNMA, the two different antagonists of L-arg. In another set of experiments, SOR and rats with BUO were given L-arg preoperatively (that is, 24 hr prior to study). Both groups of rats had significantly higher GFR and ERPF values and lower MAP and RVR than control rats. Sham-operated rats given NwNAME 24 hours prior to study had significantly lower GFR and ERPF and higher MAP and RVR than untreated rats. Rats with BUO given NwNAME prior to obstruction had no measurable renal function and had significantly higher values for MAP after release of obstruction. These studies confirm the role of L-arg administration, and presumably EDRF, in the regulation of MAP and renal function in sham-operated rats. The results of this study also suggest decreased availability of arginine for EDRF synthesis in rats with BUO.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Cytochrome P-450 pathway in renal function of normal rats and rats with bilateral ureteral obstruction.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) are decreased and mean arterial pressure (MAP) and renal vascular resistance (RVR) are increased after unilateral release of bilateral ureteral obstruction (BUO) of 24 hr duration. An imbalance between vasoconstrictor and vasodilator substances may explain these hemodynamic changes. We examined the role of the cytochrome P-450 pathway in this setting. After unilateral release of BUO, GFR and ERPF (ml/min/kg body wt) were significantly lower in these rats than in sham-operated rats (SOR) 1.14 +/- 0.09 vs 6.7 +/- 0.5 and 3.09 +/- 0.2 vs 23.5 +/- 3.4, respectively). BUO rats had significantly higher MAP (mm Hg) and RVR (mm Hg/ml/min/kg body wt) than SOR (155 +/- 5 vs 120 +/- 1 and 29.1 +/- 1.7 vs 3.2 +/- 0.4, respectively). SOR given 3-methylcholanthrene and beta-naphthoflavone to induce the cytochrome P-450 system had no significant changes in renal function, RVR, or MAP. SOR given ketoconazole to inhibit the cytochrome P-450 system had significantly lower GFR (4.8 +/- 0.5) than temporal control rats without significant changes in ERPF (21.2 +/- 4.6), MAP (127 +/- 6), or RVR (4.2 +/- 0.9). Rats with BUO given ketoconazole had lower but not significantly different GFR (0.84 +/- .1) and ERPF (2.61 +/- .4) than BUO controls. Values for MAP did not differ in BUO rats given ketoconazole versus BUO temporal controls. BUO rats given 3-methylcholanthrene and beta-naphthoflavone had significantly higher GFR and ERPF (2.01 +/- 0.24 and 6.66 +/- 1.36, respectively) and significantly lower RVR (14.7 +/- 3.9) than control rats with BUO; MAP was unchanged. Microsomal preparations from indomethacin-treated isolated kidneys obtained from BUO rats when compared with preparations obtained from SOR had significantly less activity of the P-450 cytochrome-dependent omega/omega-1 hydroxylase (103 +/- 6 vs 130 +/- 7 pmol hydroxyeicosatetraenoic acids produced per mg of protein/min, P < 0.02) and the P-450 cytochrome-dependent epoxygenase (11 +/- 0.3 vs 30 +/- 4 pmol lipoxyeicosatrienoic acids produced per mg of protein/min, P < 0.04). Indomethacin-treated microsomes prepared from kidneys of BUO rats converted significantly less 14C-arachidonic acid through the P-450-dependent hydroxylases (13.5 +/- 0.8 vs 17.0 +/- 0.1% of 14C-arachidonic acid converted to 19- and 20-hydroxyeicosatetraenoic acids, P < 0.02), and significantly less through the epoxygenases (1.4 +/- 0.4 vs. 3.8 +/- 0.5% of 14C-arachidonic acid converted to epoxyeicosatrienoic acids).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Subdiaphragmatic vagotomy in rats induces systemic hypertension and sodium retention.

We examined the acute effects of bilateral subdiaphragmatic vagotomy (BSV) on blood pressure and renal function in female Sprague-Dawley rats. Mean arterial pressure was greater (p < 0.0001) in rats with BSV than in sham-operated rats (SOR). Rats with BSV had a significantly lower effective renal plasma flow (p < 0.01), total sodium excretion (p < 0.005), fractional sodium excretion (p < 0.01), urine flow (p < 0.01), and fractional excretion of water (p < 0.02) than SOR. The glomerular filtration rate was not significantly different between the 2 groups of rats. Plasma potassium was greater in rats with BSV than in SOR (p < 0.02). Pretreatment with an inhibitor of the angiotensin-converting enzyme prevented the above changes in rats with BSV. Changes in renal function and mean arterial pressure could not be attributed to antidiuretic hormone since plasma levels of antidiuretic hormone were lower in rats with BSV than in SOR (p < 0.002). In addition, the activity of the sympathetic system was decreased in rats with BSV, as suggested by the lower plasma levels of epinephrine (p < 0.003) and norepinephrine (p < 0.02) and the significantly lower renal tissue concentrations of norepinephrine (p < 0.03). No significant changes in renal tissue concentrations of acetylcholine or choline, its precursor, were observed in BSV rats when compared to SOR, suggesting a lack of renal parasympathetic innervation. Plasma renin activity was lower in rats with BSV (p < 0.02) than in SOR, but this effect was blunted in rats given an angiotensin-converting enzyme inhibitor prior to BSV.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Effects of dietary protein on eicosanoid production and on the activity of related enzymes in glomeruli and tubules.

Glomeruli obtained from rats fed a high-protein diet for 8 weeks produce increased amounts of eicosanoids due to greater activity of both PE-specific phospholipase A2 and cyclooxygenase. Eicosanoid synthesis in response to angiotensin II is also greater in glomeruli from rats fed a high-protein diet when compared to rats fed a low-protein diet. There was also increased synthesis of eicosanoids in medullary/papillary tubules but not in proximal cortical tubules of rats fed a high-protein diet. This appears to be due to increased activity of PC-specific phospholipase A2 and cyclooxygenase in medullary/papillary tubules.

Animals↗
PubMed1992

Effects of probucol in renal function and structure in rats with subtotal kidney ablation.

Probucol is a bisphenolic compound that lowers serum cholesterol and also has potent antioxidant properties. The present studies examined the effects of probucol administration on renal function and structure in a rat model of subtotal renal ablation. After subtotal nephrectomy, rats were fed an isocaloric rat chow diet containing 22.8% protein with or without the addition of 1% probucol. After 4 weeks, clearance studies were performed for determination of glomerular filtration rate (inulin clearance) and effective renal plasma flow (paraaminohippurate clearance). After completion of clearance studies and measurements of arterial blood pressure, the animals were exsanguinated and renal tissue was obtained for histologic evaluation. There were no differences in body weight, hematocrit, and blood pressure between the two groups of rats 4 weeks after subtotal nephrectomy. Rats with a remnant kidney given probucol had a significantly lower serum cholesterol level (47.4 +/- 5.3 mg/dl vs 87.2 +/- 10.4 mg/dl) and urea nitrogen level (40.7 +/- 3.2 mg/dl vs 63.6 +/- 8.1 mg/dl) than the control group. Rats given probucol also had significantly greater values for inulin clearance and clearance of paraaminohippurate and significantly less proteinuria than control rats. Also, rats with a remnant kidney given probucol had a significantly greater number of normal glomeruli (6.2% +/- 2.1% vs 1.1% +/- 0.9%) and a lesser number of severely affected glomeruli, grades III and IV (26.0% +/- 5.9% vs 50.9% +/- 9.1%) than rats with a remnant kidney not given probucol. Tubulointerstitial changes also were significantly less in rats with a remnant kidney given probucol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Changes in lipid environment decrease Na, K-ATPase activity in obstructive nephropathy.

Unilateral ureteral obstruction markedly alters sodium and water reabsorption by the affected kidney. These abnormalities may be due, at least in part, to decreased Na,K-ATPase activity in various segments of the nephron during obstruction. The reason for this decreased activity has, however, remained speculative. The present study examines the potential mechanisms underlying the decreased Na,K-ATPase activity in obstruction. The Na,K-ATPase activity was markedly reduced in basolateral membrane vesicles prepared from the cortex of the obstructed kidney of rats with unilateral ureteric obstruction of 24 hours duration when compared to basolateral membrane vesicles from contralateral kidneys of the same rats or to basolateral membrane vesicles from kidneys of sham operated animals. However, no such difference was present three days post-release of unilateral ureteric obstruction. When basolateral membrane vesicles were incubated with sodium dodecyl sulphate to permeabilize the vesicles, no difference in the proportion of enzyme latency was detected between the basolateral membrane vesicles from obstructed kidneys and those from sham operated rats. Immunoblotting with antibodies to the alpha subunit of Na,K-ATPase revealed equal amounts of enzyme in the basolateral membrane vesicles from contralateral kidneys, obstructed kidneys and sham operated rats. When incubated with liposomes under conditions conducive to fusion and lipid exchange the activity of Na,K-ATPase in basolateral membrane vesicles from obstructed kidneys was reconstituted almost to normal levels. This increase in enzyme activity did not occur in basolateral membranes from contralateral kidneys or in membranes from kidneys of sham operated rats incubated in the same manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1991

Localization and polar distribution of several G-protein subunits along nephron segments.

Guanine nucleotide binding proteins (G-proteins) are heterotrimeric proteins involved in signal transduction in epithelia. In addition to possessing a polarized epithelium the nephron is composed of well defined segments, each with distinct receptors, transporters and other functions. Since different G-proteins interact with different receptors, a differential distribution of the various G-protein subunits would be expected. To investigate this possibility, polyclonal antipeptide antibodies to several G-protein subunits were used to examine the distribution of these proteins in nephron segments and their localization to apical or basal membrane domains. Immunoblotting of cortical membrane vesicles demonstrated the presence of G-proteins in both the brush border and basolateral membrane. Staining with G alpha common and G alpha s antibodies demonstrated more of these G-protein subunits in the brush border than basolateral membrane. G-protein beta subunits were also present in greater quantity in brush border membranes. Immunocytochemical analysis demonstrated good antigenic preservation and basically confirmed the results of immunoblotting of renal cortex. G-proteins were also found to be differentially distributed in the medulla, the amounts increasing with proximity to inner medulla. Only G alpha s and G beta subunits were demonstrated in glomeruli, but all subunits examined were detected in brush borders of proximal and apical membrane of distal tubules in cortex. In outer medulla G alpha s was detected in both basolateral and brush borders of some tubules and only brush borders of others, G alpha i2 and G beta were found in brush border and G alpha i3 was not detected in this area.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Evidence for two distinct and functionally important sites of enhanced thromboxane production after bilateral ureteral obstruction in the rat.

1. After bilateral ureteral obstruction there is an enhanced production of thromboxane A2 by the kidney which contributes to a decline in renal function. An acute interstitial macrophage infiltrate also occurs. 2. The relative contribution of infiltrating cells and intrinsic renal cells to the enhanced production of thromboxane A2 by the hydronephrotic kidney were determined. The effects of both irradiation and subsequent administration of the thromboxane synthesis inhibitor OKY-046 on both thromboxane B2 excretion and renal function were examined in rats with 24 h bilateral ureteral obstruction. 3. Irradiation effectively prevented the leucocyte infiltrate after bilateral ureteral obstruction (1.2 +/- 0.8 x 10(5) versus 27.1 +/- 0.1 x 10(5) cells/g of cortex, n = 4 in each group), resulted in a significantly higher inulin clearance (2.78 +/- 0.27 versus 1.49 +/- 0.17 ml min-1 kg-1 body weight, n = 7 and n = 8, respectively, P less than 0.001) and reduced thromboxane B2 excretion to 39% of non-irradiated values. Subsequent administration of OKY-046 to previously irradiated animals further reduced thromboxane B2 excretion to 20% of the value in non-irradiated rats with bilateral obstruction and further increased inulin clearance to 3.34 +/- 0.26 ml min-1 kg-1 body weight. 4. Glomerular macrophage numbers were decreased after bilateral ureteral obstruction (in contrast to the interstitium). However, glomeruli isolated from rats with 24 h bilateral ureteral obstruction exhibited enhanced production of thromboxane B2 compared with sham-operated control rats (855.6 +/- 31.1 versus 392.2 +/- 25.5 pg 60 min-1 mg-1 of protein, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The recovery of renal function in rats after release of unilateral ureteral obstruction: the effects of moderate isotonic saline loading.

Following 24 h of ureteral obstruction in the rat, renal blood flow and glomerular filtration rate are markedly depressed. The effect of saline loading on post-obstructive glomerular filtration (GFR) was studied in 15 female Sprague-Dawley rats in the awake state, 4 h following the release of 24 h of unilateral ureteral obstruction. Group I (n = 8) received 39 microliters min-1 of 0.9% saline only for 1 h prior to study and Group II (n = 7) received 78 microliters min-1 of 0.9% saline for the whole 4 h prior to study. The Cin and CPAH of the post-obstructed kidney were significantly reduced over control values in both groups. Saline loading (Group II) resulted in an improvement in Cin in the post-obstructed kidney compared with group I (3.22 +/- 0.14 vs. 2.19 +/- 0.14 ml/min/kg BW, P less than 0.001). This was independent of any change in CPAH. In two further groups of rats the saline loading protocol was shown to cause a rise in the excretion of urinary cGMP in the post-obstructed kidney, but not the contralateral control kidney. In addition, administration of exogenous atriopeptin (1-24) to non-saline loaded animals resulted in a qualitatively similar alteration in renal function to saline loading, namely a rise in Cin and an increase in excretion of cGMP by the post-obstructed kidney, and no change in CPAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mechanism of enhanced eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction.

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.

6-Ketoprostaglandin F1 alpha↗