Exaggerated renal thromboxane and prostaglandin release by angiotensin II in suprarenal aortic coarctation hypertension

The ability of angiotensin II and arachidonic acid to release immunoreactive prostaglandins into venous and ureteral effluents of rabbit isolated perfused kidneys was examined 7 days after suprarenal aortic coarctation (SRAC) or sham operation (SHAM). Renal vascular responses to angiotensin II were significantly enhanced in SRAC and accompanied by an enhanced venous efflux of bioassayable prostaglandins. Angiotension II-induced release of immunoreactive PGE2, PGF2 alpha, 6-keto PGF1 alpha and TxB2 into the venous effluent was exaggerated in SRAC. As angiotensin II did not stimulate TxB2 efflux in the SHAM group the induction of TxB2 release by SRAC is particularly noteworthy. These changes in eicosanoid release in response to angiotensin II were not mimicked by arachidonic acid administration. These results suggest that in renovascular hypertension angiotensin II-induced prostaglandin release is primarily augmented in the vascular compartment and is consistent with the sensitivity of renal function to cyclooxygenase inhibitors in renovascular hypertension.     

Compartmental prostaglandin release by angiotensin II and arginine-vasopressin in rabbit isolated perfused kidneys

The compartmental effects of angiotensin II (AII) and arginine-vasopressin (AVP) on renal prostaglandin (PG) formation were studied in the isolated perfused kidney of the rabbit by superfusion bioassay of venous and ureteral effluents (VE and UE) and radioimmunoassay (RIA). Comparable results were obtained with either bioassay or RIA when used to quantitate renal PG release. The effects on PG release into the VE were similar for AII and AVP, as were their pressor responses. However, their effects on PG release into the UE differed markedly. AII resulted in a 6-fold greater urinary efflux than venous of bioassayable PGs, whereas AVP-induced PG release into UE was slightly less than PG efflux into the VE at all doses of the peptide. The profile of released PGs varied according to the sampling source (VE or UE). Moreover, each peptide released a similar profile of PGs at all doses, i.e. UE PGE2 greater than PGF2 alpha greater than 6-keto PGF1 alpha; VE PGE2 greater than 6-keto PGF1 alpha greater than PGF2 alpha (TxB2 was not detected in either effluent). Thus, renal vascular PG release is similar for the vasoactive peptides, AII and AVP, whereas the urinary efflux of PGs is considerably greater in response to AII.     

Prostaglandins and thromboxane in the delayed phase of shock induced by Serratia marcescens endotoxin.

The cardiovascular and metabolic effects of an endotoxin derived from Serratia marcescens were examined in anaesthetized, spontaneously-breathing cats. There was a marked initial elevation of right atrial pressure (the result of pulmonary vasoconstriction) and decreases in systemic arterial pressure and in arterial PO2. The 'delayed' effects of endotoxin shock in this species (1-8 h) consisted of a reduced cardiac output and decreased urinary excretion. Blood pressure and myocardial contractility (assessed from measurement of left ventricular (LV) dP/dt and LV end-diastolic pressure) were maintained throughout this phase. There was evidence of a metabolic (lactic) acidosis largely compensated by hyperventilation. Plasma levels (both arterial and mixed venous blood samples) of prostaglandin (PG)E2, PGF2 alpha, 6-keto PGF1 alpha and thromboxane (TX)B2 were measured by radioimmunoassay techniques. Endotoxin administration caused substantial increases in the plasma levels of all four derivatives of arachidonic acid, especially between 1 and 6 h. Separation of the endotoxin-treated cats into survivors and non-survivors showed that the non-survivors had significantly higher circulating levels of PGE2, TXB2 and PGF2 alpha. It is suggested that TXB2 and PGF2 alpha might contribute to some of the detrimental effects of endotoxin (e.g. pulmonary, mesenteric, renal vasoconstriction; platelet aggregation with resulting organ failure) and that prostacyclin may be beneficial in endotoxin shock in this species.     

A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury

The effects of DP-1904, a thromboxane (TX) A2 synthase inhibitor, on renal function were investigated by analysis of prostanoid metabolism in hydronephrotic and ischemic rat kidney models, and in isolated perfused normal and hydronephrotic rat kidneys. The increase in production of TXB2 in hydronephrotic or ischemic kidneys was significantly suppressed by intraperitoneal DP-1904 (10 mg/kg), with the 6-keto-prostaglandin F1 alpha to TXB2 ratio being significant increased. Urine volume, glomerular filtration rate and renal plasma flow were all improved. DP-1904 (0.3 micrograms/min) blocked the effects of infused arachidonic acid on isolated perfused normal rat kidneys thus reducing TXB2 levels and perfusion pressure but the pressor response to norepinephrine or angiotensin II remained unchanged. In isolated perfused hydronephrotic rat kidneys, DP-1904 suppressed the increase in perfusion pressure and TXB2 production caused by platelet-activating factor. These findings suggested that DP-1904 improved renal failure by specifically inhibiting TXA2 production.     

Total profiling by GC/NICIMS of the major cyclo-oxygenase products from antigen and leukotriene-challenged guinea-pig lung

Separation and quantitation of all the major cyclo-oxygenase products in perfused guinea-pig lungs challenged with antigen or leukotrienes C4 and D4 were achieved using a novel combined capillary column gas chromatography/negative ion chemical ionization mass spectrometric (GC/NICIMS) method. In descending order of magnitude, unchallenged lungs released thromboxane B2 (TXB2) plus its pulmonary metabolite (TXDK) greater than 6-keto-PGF1 alpha plus its 13,14-dihydro-15-keto metabolite (K2H1F1 alpha) greater than PGE2 plus PGF2 alpha greater than PGD2; after ovalbumin anaphylaxis there were increases of X 26 in TXB2 plus TXDK, X 28 in PGD2 and histamine (measured fluorometrically) but of only X 3 in 6-keto-PGF1 alpha plus K2H2F1 alpha and PGE2 plus PGF2 alpha. FPL55712 treatment greatly reduced the release of TXB2 and 6-keto-PGF1 alpha and their metabolites (showing this to be a secondary effect mediated by leukotriene action) but did not affect PGD2 output. LTC4 and LTD4 themselves induced the release of TXB2 and TXDK, as did bradykinin, but neither substance caused appreciable PGD2 release. Aside from illustrating the great value of the GC/NICIMS method for simultaneously determining all cyclooxygenase products, the main conclusions are: (i) PGD2 may be an in vitro marker for activation of lung inflammatory cells; (ii) prostacyclin and thromboxanes are actively metabolized in situ in the lung; and (iii) 'pathological subversion' of pulmonary function by anaphylaxis, leukotrienes or bradykinin principally causes thromboxane release from unknown target cells, with a smaller release of prostacyclin which may be compensatory in nature.     

Failure of anti-inflammatory steroids to inhibit prostaglandin release from the hydronephrotic rabbit kidney

The release of prostaglandins E2, F2 alpha, I2 and thromboxane A2 from isolated perfused normal and hydronephrotic rabbit kidneys was investigated by extraction and radioimmunoassay. In both types of kidneys, basal PG efflux increased with time and was not altered by co-perfusion with dexamethasone or hydrocortisone. Several vasoactive substances at 1 to 4 micrograms (e.g., bradykinin, angiotensin II, substance P, noradrenaline and vasopressin) caused release of additional amounts of prostaglandins. PGE2 and 6-keto PGF1 alpha were the major prostanoids detected, but substantial amounts of PGF2 alpha were also found. Thromboxane A2 was not released from normal kidneys. In hydronephrotic kidneys there was greatly augmented release of prostaglandins E2 and I2, some increases in PGF2 alpha, and the appearance of substantial amounts of thromboxane A2 (measured as immunoreactive TXB2) when the kidneys were challenged with angiotensin, bradykinin and vasopressin, and smaller augmentation of the response to noradrenaline and substance P. There was no evidence that these evoked increases in renal PG output could be inhibited by dexamethasone or hydrocortisone. Some explanations for the failure of steroids to alter prostanoid metabolism from arachidonate in rabbit kidney are discussed, and it is proposed that there are clear exceptions to the concept that steroids inhibit prostaglandin generation in intact tissues.     

A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy.

Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.     

Effects of a small dose of ethanol and calcium carbimide-induced acetaldehyde intoxication on human platelet aggregation, associated thromboxane formation and urinary excretion of 2,3-dinor-6-keto prostaglandin F1 alpha

We studied ADP-induced platelet aggregation, associated thromboxane B2 (TXB2) formation, urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto prostaglandin F1 alpha (2,3-dinor-6-keto PGF1 alpha) and formation of malondialdehyde in 10 healthy volunteers after ingestion of a small dose of ethanol (0.25 g per kg of body weight) and calcium carbimide (50 mg). Platelet aggregation in platelet-rich plasma (PRP) was suppressed (p less than 0.05) by ethanol, but no change occurred in platelet TXB2 formation. Ingestion of calcium carbimide caused significant elevations in blood acetaldehyde (p less than 0.001) and ethanol (p less than 0.05) levels, but acetaldehyde did not influence platelet aggregability or the aggregation-associated TXB2 formation. However, calcium carbimide per se significantly (p less than 0.05) elevated TXB2 formation. No effects were found on plasma malondialdehyde levels and urinary excretion of 2,3-dinor-6-keto PGF1 alpha. These observations indicate that a small dose of ethanol attenuates platelet aggregation without any significant effect on aggregation-associated TXB2 formation. By contrast, ingestion of calcium carbimide per se may enhance TXB2 formation.     

Disposition Characteristics of Protein Drugs in the Perfused Rat Kidney

The renal disposition characteristics of ¹¹¹In-labeled neocarzinostatin (NCS), soybean trypsin inhibitor (STI), and superoxide dismutase (SOD) were studied in the perfused rat kidney. In a single-pass indicator dilution experiment, venous and urinary recovery profiles and tissue accumulation of proteins were determined under filtering or nonfiltering conditions. In the nonfiltering kidney perfusion experiment, no significant tissue accumulation was observed, suggesting minimal uptake from the glomerular and peritubular capillary sides. Therefore, tissue recovery corresponded to that with tubular reabsorption after glomerular filtration. The total amount of NCS or STI being filtrated through glomeruli, the sum of tissue and urinary recoveries, was similar to that of inulin, but that of SOD was about half. Similarly, the steady-state distribution volumes (V _d) of NCS and STI obtained by moment analysis of their venous outflow curves were similar to that of inulin, while the V _d value of SOD was significantly lower. These results suggest the restricted passage of SOD through the glomerular and postglomerular capillary wall. The tubular reabsorption ratio of proteins against the total filtrated amount decreased with an increase in the administered dose, suggesting nonlinearity of reabsorption. SOD had the largest reabsorption ratio. Thus, this experimental system is useful for quantitative analysis of renal disposition of proteins.     

Effects of suprofen on renal function in patients with rheumatoid arthritis

Suprofen is a new potent analgesic with antiinflammatory properties that appears to inhibit prostaglandin synthetase in a tissue-selective manner, having relatively little effect on the kidneys of experimental animals. The effects were studied of one week of treatment of rheumatoid arthritis patients with suprofen or ibuprofen on Na+ and K+ excretion, creatinine clearance, urinary enzymes that are markers for tubular damage, and urinary prostaglandins such as PGE2 and 6-keto PGF1 alpha (a stable metabolite of prostacyclin). Neither compound caused changes in renal function related to the week of treatment, but significant decreases in prostaglandins were observed: this change was fully reversible after discontinuation of the drug.     

人参多糖对兔肝缺血/再灌注损伤时TXB2/PG1α平衡的调控作用

目的:观察肝缺血/再灌注损伤时血栓素B2(Thromboxane B2,TXB2)、前列环素F1α(Prostaglandin F1α,PGF1α)、TXB2/PGF1α比值变化和人参多糖的干预作用。方法:30只家免,随机均分为对照组(C组)、缺血/再灌注组(IR组)和人参多糖组(GP组)。分别检测三组缺血前10min、缺血45min及再灌注45min后血浆中TXB2、PGF1α、ALT及TXB2/PGF1α比值的变化,电镜下观察肝细胞超微结构的改变。结果:IR组血浆TXB2各对应时间点浓度均较C组明显升高,PGF1α含量再灌注45min时较缺血前显著下降,TXB2/PGF1α比值明显增高,肝细胞超微结构显著异常。使用人参多糖注射液后,血浆TXB2浓度较IR组同期水平降低,PGF1α再灌注45min显著高于IR组同期水平,TXB2/PGF1α显著低于IR组,尤以再灌注45min为著,肝细胞超微结构异常较IR组有所减轻。结论:人参多糖可通过调节TXB2/PGF1α之间的平衡,改善肝脏微循环,从而防治肝缺血/再灌注损伤。     

The protective effect of prostacyclin on adriamycin-induced apoptosis in rat renal tubular cells

Adriamycin-induced nephrosis in rats is a commonly used experimental model for pharmacological studies of human chronic renal diseases. Adriamycin-induced apoptosis of renal tubular cells has been reported in adriamycin-treated rats. In addition, prostacyclin (PGI(2)) is known to have various protective effects on many kinds of cells. To investigate the protective effect of PGI(2) on cells undergoing adriamycin-induced apoptosis, this study selectively augmented PGI(2) production via adenovirus-mediated transfer of genes for cyclooxygenase-1 (COX-1) and prostacyclin synthase (PGIS) (two key enzymes of PGI(2) synthesis) to renal tubular cells. This PGI(2) overexpression protected rat renal tubular cells from adriamycin-induced apoptosis. Ad-COX-1/PGIS transfection was found to reduce the adriamycin-stimulated activities of caspase-3 and caspase-9, inhibit adriamycin-induced release of cytochrome c, elevate the expression of Bcl-x(L), and suppress the activation and translocation of nuclear factor-kappaB (NF-kappaB) in adriamycin-treated renal tubular cells. Our results reveal that selective augmentation of PGI(2) production can protect rat renal tubular cells from adriamycin-induced apoptosis via the NF-kappaB signaling pathway. This implies the therapeutic potential of combined COX-1 and PGIS gene transfer in gene therapy for chronic renal diseases.     

Glucuronidation of 1-naphthol and excretion into the vein in perfused rat kidney.

UDP-glucuronosyltransferase is expressed in the proximal convoluted tubular cells of rat kidney. Kidney perfusion with a Krebs-Henseleit buffer containing 1-naphthol was performed to estimate the dynamics and disposition of the glucuronide conjugate formed in the epithelial cells of the renal tubules. When 1-naphthol was injected into the renal artery, and the perfusate from the renal vein was returned to a reservoir and recirculated through the kidney preparation (recirculating perfusion), most of the 1-napthol was immediately excreted into the vein as a glucuronide conjugate and its concentration increased rapidly. In contrast, the 1-napthol glucuronide appeared more slowly in the urine. 1-Naphthol was also injected during the initial 5 min of perfusion under single-pass perfusion conditions (single-pass perfusion) in situ, and the metabolite and parent compound in the venous perfusate and in urine were assayed. Under this condition, most of the 1-naphthol glucuronide was excreted into the renal vein, and not urine. Phenol UDP-glucuronosyltransferase was highly induced in the rat kidney by beta-naphthoflavone treatment. Moreover, the amount of 1-naphthol glucuronide excreted in the renal vein was increased 2.7-fold in the perfused kidney of beta-naphthoflavone-treated rats, but the amount in the urine was not significantly increased under singlepass perfusion conditions. These results indicate that the kidney can glucuronidate phenolic xenobiotics in epithelial cells of the tubules and excrete the resultant glucuronide into the renal vein.     

Roles of endogenous prostacyclin and thromboxane A2 in the ischemic canine heart

The ability of the ischemic heart to release prostacyclin (PGI2) and thromboxane A2 (TXA2) was studied, together with the effects of these substances on the ischemic myocardium in open-chest dogs. We measured the plasma levels of 6-keto-PGF1 alpha and TXB2--which are stable metabolites of PGI2 and TXA2, respectively--as well as lactate and coronary venous blood flow. The dogs were divided into three groups of eight animals which received indomethacin (5 mg/kg), (E)-3-[4-l-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046) (1 mg/kg), or the vehicle. A transient increase in 6-keto-PGF1 alpha was observed in the great cardiac vein 5 min after the ligation of the left anterior descending coronary artery (LAD). TXB2 and lactate increased 30 and 15 min, respectively, after the ligation. Indomethacin prevented significant increases in 6-keto-PGF1 alpha and TXB2, but accelerated the lactate release. OKY-046 prevented significant increases in TXB2 and lactate release, but did not counteract the increase in 6-keto-PGF1 alpha. Although coronary venous flow decreased significantly 5 min after the ligation in every group, the flow returned to the preligation level 15 min after the ligation in the OKY-046 and the vehicle groups. Thus, we have demonstrated the release of PGI2 and TXA2 from the ischemic heart and suggest beneficial effects of PGI2 and of a selective inhibitor of thromboxane synthetase on the ischemic myocardium.     

Metabolism of prostaglandin E2 in the isolated perfused kidney of the rabbit

In the Krebs-perfused rabbit isolated kidney, [³H]PGE₂ (5 μCi, 165 Ci/mmole) was infused intra-arterially for 5 min; venous and urinary effluents were collected every 2 min for 20 min. Efflux of radioactive material peaked at 8 min and declined thereafter. The kidney retained 35% of the infused ³H. Samples were extracted for acidic lipids; PGE₂, PGF_2α and metabolites were separated by TLC and quantified by a radiometric method. Efflux of [³H]PGF_2α into urinary and venous outflows increased progressively over the first 12 min and then plateaued for the remaining 4 min. By 12 min, conversion of [³H]PGE₂ to [³H]PGF_2α was 70 and 80% as determined by radiolabeled products recovered in the urinary and venous effluents respectively. Estimates of total conversion of [³H]PGE₂ to [³H]PGF_2α were 62 and 52% of the radiolabeled material exiting in the urinary and venous effluents respectively. The 15-keto and 13,14-dihydro-15-keto metabolites of [³H]PGF_2α appeared in the urine but were not found in the venous outflow. We conclude that PGE-9-ketoreductase (PGE-9KRD) activity is high in the rabbit isolated perfused kidney. Further, the extent of conversion of PGE₂ to PGF_2α and metabolism of newly formed PGF_2α may differ within the vascular and tubular compartments of the kidney. PGE-9KRD activity may be important in the regulation of renal vascular tone, compliance of veins, and salt and water balance.     

重复肾彩色多普勒超声影像特点

目的探讨重复肾彩色多普勒超声影像特点及其临床诊断价值。方法回顾15例经我院临床证实的重复肾的超声影像特点,分析其临床类型及诊断价值。结果 13例为单侧病变,2例为双侧病变。其中6例肾内有两个相互独立的肾窦高回声团,肾实质呈桥状分隔两个肾窦回声,未见明显肾盏扩张及输尿管扩张。应用CDFI观察肾门血供,均可显示双肾门。9例有不同程度的上位肾窦积水及上位输尿管扩张,合并输尿管末端囊肿3例,输尿管末端异位开口6例。结论彩色多普勒超声对重复肾有很高的诊断价值。     

Wen-pi-tang-Hab-Wu-ling-san reduces ureteral obstructive renal fibrosis by the reduction of oxidative stress,inflammation, and TGF-β/Smad2/3 signaling

Kidney fibrosis results in chronic renal disease. The current treatment of chronic renal diseases is limited to angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Recently, we found that Wen-pi-tang-Hab-Wu-ling-san (WHW) extract, which has been used to treat renal diseases in herbal medicine for a long time, plays anti-fibrogenic. Here, we investigated the role of WHW in the kidney fibrosis induced by unilateral ureteral obstruction (UUO) in mice. C57BL/6 male mice were subjected to UUO on day 0 and then administered with either WHW (2, 10, or 50 mg/kg of body weight) or vehicle orally from 1 day after UUO to finish the experiment. WHW-administration significantly mitigated the UUO-induced kidney fibrotic changes including tubular atrophy and dilatation, collagen accumulation, expansion of interstitial space and leukocyte infiltration. WHW prevented the increases of oxidative stress by the prevention of UUO-induced decreases of catalase, copper–zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD), resulting in reduced production of oxidative stress. Furthermore, WHW reduced transforming growth factor-β (TGF-β) expression and phosphorylation of Smad2/3 stimulated by UUO. In conclusion, WHW prevented kidney fibrosis following UUO by the inhibition of inflammation, oxidative stress and TGF-β/Smad2/3 signaling pathway.     

Effects of chronic treatment with caffeine on kidney responses to angiotensin II.

Previous studies demonstrate that chronic administration of caffeine causes glomerular filtration to deteriorate in rats with high-renin renovascular hypertension. A partial explanation for these findings could be that chronic administration of caffeine alters the effects of angiotensin II on the kidney. As an initial test of this hypothesis, we compared the acute effects of intrarenal infusions of angiotensin II (3 ng/min) on renal function in control rats versus rats treated with 0.1% caffeine in their drinking water for 1 week. The renal responses to angiotensin II in a group of animals receiving acute intrarenal infusions of adenosine (10 micrograms/min) were also measured to determine whether caffeine and adenosine modulated renal responses to angiotensin II in opposite directions. All studies were performed in the in situ blood perfused rat kidney. Neither caffeine nor adenosine significantly altered angiotensin II-induced changes in renal blood flow, urinary excretory function or renin release. However, caffeine augmented and adenosine attenuated the increase in filtration fraction caused by angiotensin II. The fact that caffeine potentiates angiotensin II-induced increases in filtration fraction without affecting angiotensin II-induced reductions in renal blood flow is consistent with, but does not prove, the hypothesis that chronic administration of caffeine modifies the effects of angiotensin II on the renal microvasculature. If this inference is correct, caffeine could facilitate renal damage in high-renin hypertension by exacerbating angiotensin II-induced increases in glomerular capillary hydrostatic pressure.     

Characterization of furosemide-induced activation of the renal prostaglandin system.

A detailed time course of changes in plasma renin activity (PRA), urinary prostaglandin (PG) E2, PGF2 alpha, thromboxane (TX) B2 and sodium excretion rates following furosemide was obtained in 7 women. PRA increased within the first 15 min and remained elevated all through the experiment. PGE2, PGF2 alpha, TXB2 and sodium increased simultaneously, reached a peak between 15 and 45 min after furosemide and declined thereafter. It is concluded that furosemide induces a generalized activation of the renal PG system temporally related to the increase of renin release and natriuresis.     

The effect of angiotensin I converting enzyme inhibitor (SQ 20881) on the release of prostaglandins by rabbit kidney, in vivo.

1. Prostaglandin E- and F-like material has been estimated in renal venous blood of the left kidney of anaesthetized rabbits following renal nerve section. Prostaglandins were estimated by bioassay following solvent extraction and column chromatography. 2. Electrical stimulation of the renal nerves of the left kidney to reduce renal blood flow by approximately 15% for 15 min resulted in a significant increase in the concentration of prostaglandin E-like material in the renal venous blood. The peak values were normally seen either in the last 5 min of the stimulation period or in the first 5 min after the end of the stimulation period. The concentration of prostaglandin F-like material was not significantly altered. 3. Similar reduction of renal blood flow of the left kidney by renal artery constriction also resulted in a significant increase in the concentration of prostaglandin E- but not F-like material in renal venous blood. The timing and magnitude of the response was comparable with that observed with renal nerve stimuation. 4. The effect of an angiotensin I converting enzyme inhibitor, SQ 20881, on the response to both renal nerve stimulation and renal artery constriction has been studied. The administration of the drug did not significantly reduce the release of prostaglandins from the denervated kidneys, however, the increase in prostaglandin E-like material, in response to both stimuli, was abolished. 5. The results suggest that the increase in prostaglandin E-like material released from the kidney in response to low frequency stimulation or to modest reductions in renal blood flow is dependent on the release of renin and that the effect is mediated by the formation of angiotensin II and not angiotensin I.