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Biomedical subjects

R Lacave

Publications and source records attributed to R Lacave.

At least 19 recordsLinked to original sources
PubMed1992

Cell-specific regulation of plasminogen activator inhibitor 1 and tissue type plasminogen activator release by human kidney mesangial cells.

Human mesangial cells in culture synthesize and secrete plasminogen activator inhibitor 1 (PAI-1) and tissue-type plasminogen activator (t-PA). Phorbol myristate acetate (PMA), a known activator of protein kinase C, induces a three to four-fold increase in t-PA and PAI-1 release over a period of 24 h, whereas cell-associated t-PA and PAI-1 levels remain relatively stable. A similar effect is obtained with oleylacetyl glycerol, a more physiologic protein kinase C activator. The effect of PMA is suppressed in the presence of H7, an inhibitor of cellular protein kinases, and by cycloheximide and actinomycin D, indicating a requirement for de novo protein and RNA synthesis, respectively. Northern blot analysis of PMA-treated cells reveals a rapid and transient increase in PAI-1 mRNA reaching a maximum after 4-8 h, whereas increase in t-PA mRNA levels requires 24 h. Activation of protein kinase A by addition of 8-bromocyclic AMP (8-bromo cAMP) has no significant effect on PAI-1 release but inhibits the PMA-mediated increases in PAI-1 antigen and mRNA. Addition of 8-bromo cAMP alone does not affect t-PA release. When added to PMA-stimulated cells, 8-bromo cAMP inhibits t-PA release in a dose-dependent manner, but causes a superinduction of t-PA mRNA. 8-bromo cAMP also induces a decrease in PMA-stimulated intracellular t-PA release. Similar inhibition is observed after stimulation of endogenous adenylate cyclase with prostaglandin E1 or isoproterenol. This indicates that protein kinase A activation may inhibit PMA-stimulated t-PA release via a post-transcriptional effect, e.g. inhibition of protein synthesis or activation of protein degradation. In conclusion, hormones or mediators which activate protein kinase C can stimulate t-PA and PAI-1 synthesis in human mesangial cells. Protein kinase A activation has no effect on the basal release of PAI-1 and t-PA by human mesangial cells, and, in contrast to endothelial cells, it inhibits both PMA-stimulated PAI-1 and t-PA releases. This cell-specific regulation of t-PA and PAI-1 seems to be mediated by differential transcriptional and post transcriptional mechanisms.

Blotting, Northern↗
PubMed1991

[TNF-alpha synthesis by circulating mononuclear cells in patients undergoing kidney transplantation].

In 7 patients who received renal transplant, systematic blood samples and cytoaspiration of the graft were performed every 3 days after grafting. In vitro TNF-alpha generation by circulating mononuclear cells and by cells infiltrating the graft were measured under basal conditions and after stimulation by recombinant IL-2 (50 U/ml). TNF-alpha concentration was determined by immunoradiometric assay (IRMA). Not enough cells could be collected by cytoaspiration to measure TNF-alpha concentration. In contrast, the generation of TNF-alpha by circulating mononuclear cells was detectable. It increased 24 to 48 hours before the rejection crisis and decreased after successful treatment and return of creatinin level to initial value. IL-2 increased TNF-alpha production and was more effective under normal conditions (10 to 15 fold increase) than during rejection episodes (1.3 to 2.4 fold). These results suggest that TNF-alpha is produced by mononuclear cells during rejection episodes and could be used as a marker of rejection. Further studies are required to determine its sensitivity and specificity.

Adult↗
PubMed1991

Thrombin increases proliferation and decreases fibrinolytic activity of kidney glomerular epithelial cells.

Human glomerular epithelial cells (GECs) in culture synthesize single-chain, urokinase-type plasminogen activator (SC-uPA), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) and possess specific membrane-binding sites for u-PA. Using purified 125I-alpha thrombin, we demonstrate here the presence of two populations of specific binding sites for thrombin on GECs (1.Kd = 4.3 +/- 1.0 x 10(-10) M, 5.4 +/- 1.4 x 10(4) M sites per cell, 2. Kd = 1.6 +/- 0.5 x 10(-8) M, 7.9 +/- 1.8 x 10(5) sites per cell). Purified human alpha thrombin promoted the proliferation of GECs and induced a time- and dose-dependent increase of SC-uPA, t-PA, and PAI-1 antigens released by GECs. Thrombin-mediated increase in antigen was paralleled by an increase in the levels of corresponding u-PA and PAI-1 messenger RNA. In contrast, thrombin decreased u-PA activity in conditioned medium. This discrepancy between u-PA antigen and u-PA activity was explained by a limited proteolysis of SC-uPA by thrombin, leading to a two-chain form detected by immunoblotting and that could not be activated by plasmin. Thrombin also decreased the number of u-PA binding sites on GECs (p less than 0.05) without changing receptor affinity. Hirudin inhibited the binding and the cellular effects of thrombin, whereas thrombin inactivated by diisopropylfluorophosphate had no effect, indicating that both membrane binding and catalytic activity of thrombin were required. We conclude that thrombin, through specific membrane receptors, stimulates proliferation of GECs and decreases the fibrinolytic activity of GECs both at the cell surface and in the conditioned medium. These results suggest that thrombin could be involved in the pathogenesis of extracapillary proliferation and persistency of fibrin deposits in crescentic glomerulonephritis.

Cell Division↗
PubMed1991

Aortoiliac surgery and kidney transplantation.

Between January 1980 and December 1989, we performed 407 renal transplantations. Twelve of these patients (3%) underwent aortoiliac reconstruction before (Group I, two patients), concomitant to (Group II, five patients) or after (Group III, five patients) renal transplantation. The aortoiliac lesions treated included four aneurysms and seven occlusions of the abdominal aorta and one postarteriography dissection of the iliac artery. A prosthetic graft was inserted in nine cases (75%). Endarterectomy was performed in the three other cases (25%). Four of five patients in Group III were operated on without any particular protection for the transplant. There were no postoperative deaths in Groups I and III. In Group II, one patient died of infection secondary to a urinary tract fistula. Early and late vascular morbidity (renal artery stenosis, occlusion of aortoiliac reconstruction, anastomotic false aneurysm) occurred with equal frequency in the three groups. Renal transplantation in patients having already undergone aortoiliac surgery and, conversely, aortoiliac reconstruction in the renal transplant patient, are possible without any particular technical precautions with minimal mortality and kidney morbidity. Simultaneous renal transplantation and aortoiliac reconstruction carries a significant risk of infection and a two-stage procedure should be considered in this situation.

Adult↗
PubMed1991

Stable cell line of T-SV40 immortalized human glomerular visceral epithelial cells.

Human subcultures (third passage) of glomerular visceral epithelial cells (VEC) isolated from one month old kidney were successfully transfected by two recombinant plasmids containing the cloned oncogenes from the simian virus 40 large T antigen and H-ras gene. One postcrisis cell clone (56/10 A1) was selected, propagated and characterized. One hundred percent of the 56/10 A1 cells (current passage greater than 100th; doubling time 30 hrs) expressed the nuclear T-SV40 antigen assayed by IF; the cells failed to express H-ras (RNA blot analysis). Immortalized cells were morphologically and phenotypically compared to parental cell type (third passage). Phenotypic characterization of the 56/10 A1 cells was achieved using indirect immunofluorescence (IF) and immunogold silver staining coupled to bright field and epipolarization microscopy. Both parental and 56/10 A1 cells displayed positivity for cytokeratin, CALLA and PHM5, whereas von Willebrand factor was not detected in the two cell types. Since we have previously shown that human glomerular epithelial cells in culture synthetize plaminogen activator (PA) related compounds, we investigated the secretion pattern of these products in parental and transfected cells. Zymographic analysis of secreted PA related compounds revealed production of free urokinase (u-PA) and type 1 plasminogen activator inhibitor (PAI-1) complexed to tissular plasminogen activator (t-PA). Finally, in the transfected cells, increased cGMP generation under atrial natriuretic factor (ANF) stimulation agreed with previous work performed on nontransfected human VEC. In conclusion, the establishment of a human permanent cell line which retains most of the phenotypic features of parental glomerular visceral epithelial cells should represent a new tool to study human glomerular cell functions.

Antigens, Viral, Tumor↗
PubMed1991

Proopiomelanocortin gene expression in normal and tumoral human lung.

Proopiomelanocortin (POMC) gene expression is not restricted to the pituitary corticotroph cell, but also takes place in many normal and tumoral nonpituitary tissues. In contrast, the ectopic ACTH syndrome is a rare event. Because it is most often associated with lung tumors, we specifically studied this tissue, analyzing the different forms of POMC RNAs in normal specimens as well as in various types of tumors. The endocrine nature of the tumors was assessed by both histological examination and measurements of secretogranin-I fragments in the tissue extracts. POMC RNA was first detected by Northern blot analysis; its absolute amounts and its various molecular forms were more precisely quantified and discriminated by S1 mapping studies using a single stranded DNA probe located at the 5' end of exon 3. In five bronchial carcinoid tumors associated with the ectopic ACTH syndrome, a highly predominant, if not single, POMC RNA identical to the 1200-nucleotide (nt) pituitary message was present, the high amounts of which were correlated with those of POMC peptides in the same tissues. In five bronchial carcinoid tumors not associated with the ectopic ACTH syndrome, the same message was detected (four of five), with a second, often predominant, short RNA of about 800 nt (five of five), and the overall amounts of POMC RNAs were low. Similar patterns of POMC RNAs were observed in squamous cell tumors, adenocarcinomas, and normal lung, where the short 800-nt RNA tended to be predominant. These results show that POMC gene expression can be demonstrated in normal lung tissue and in all types of lung tumors. The ectopic ACTH syndrome only occurs with tumors capable of generating high amounts of the pituitary-like message, a phenomenon that seems to be restricted to an occasional tumor with features of neuroendocrine differentiation.

Carcinoid Tumor↗
PubMed1990

Nordihydroguaiaretic acid inhibits urokinase synthesis by phorbol myristate acetate-stimulated LLC-PK1 cells.

Protein kinase C (PKC) activation is regulated by Ca2+, phospholipids, diacylglycerol (DAG) and fatty acids. Phorbol myristate acetate (PMA) which mimics the effect of DAG on PKC induces transcriptional activation of the urokinase-type plasminogen activator (u-PA) gene in LLC-PK1 cells. We examined in the present work the relationships between PKC activity, fatty acids, and u-PA synthesis in this cell line. We showed that H7, an inhibitor of PKC, inhibited the PMA-induced u-PA synthesis by LLC-PK1 cells. PMA-induced u-PA synthesis was enhanced by eicosatetraynoic acid (ETYA), a competitive inhibitor of both the lipoxygenase and cyclooxygenase pathways and inhibited by nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase pathway. Three other unrelated lipoxygenase inhibitors (phenidone 100 microM, BW755 50 microM and diethylcarbamazine 50 microM) had no effect on u-PA biosynthesis. Two polyunsaturated fatty acids other than ETYA, arachidonic acid and linoleic acid, also potentiated the PMA effect and a lipoxygenase derivative, 12 hydroxyeicosatetraenoic acid (12 HETE), did not modify the basal and PMA-stimulated u-PA syntheses. PKC activity purified from cytosol of LLC-PK1 cells was stimulated by addition of 16 nM PMA in vitro and this effect was blunted by simultaneous addition of 5 microM NDGA. By Northern blot analysis using a pig u-PA cDNA probe we found that PMA increased the steady state level of u-PA mRNA after 2 h of incubation and that NDGA inhibited this effect. These data suggest that NDGA inhibits PMA-stimulated PKC activity in intact cells leading to a decrease of u-PA mRNA level and u-PA biosynthesis in PMA-stimulated LLC-PK1 cells. Polyunsaturated fatty acids have opposite effects.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Linkage study of a large family with autosomal dominant polycystic kidney disease with reduced expression. Absence of linkage to the PKD 1 locus.

We describe a large three generation family with autosomal dominant polycystic kidney disease (PKD). Ultrasonographic screening of 60 family members revealed 20 individuals, whose age ranged from ten to eighty years, with one or several cysts in only one kidney and 7 individuals with cysts in both kidneys. Transmission of unilateral cysts seems to be autosomal dominant, although there are some generation gaps. Linkage studies with several markers of the PKD1 locus on the short arm of chromosome 16 showed no linkage with the disease. Lod scores for linkage between the disease and the most informative marker 3'HVR were computed using different penetrance models and several hypotheses concerning the clinical status of individuals with unilateral renal cysts. Results varied from Z = 1.31 to Z = -21.47 (theta = 0). Smith's test of heterogeneity gave a conditional probability of non-linkage between 0.9 and 1.0. We conclude that this family presents a form of autosomal dominant PKD with reduced penetrance and no linkage to the PKD1 locus on the short arm of chromosome 16. Other hypotheses, such as the existence of two distinct hereditary diseases in this large family, or neomutation in one branch of the family associated with a high frequency of isolated renal cysts, are also considered.

Family↗
PubMed1990

Thrombin regulates components of the fibrinolytic system in human mesangial cells.

Besides its procoagulant activity, thrombin has been shown to stimulate cell proliferation and to regulate the fibrinolytic pathway. We report here the effect of purified human alpha thrombin on the synthesis of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by cultured human mesangial cells. Thrombin (0 to 2.5 U/ml) increased in a time- and dose-dependent manner the production of t-PA and PAI-1 (2- to 3-fold increase of secreted t-PA and PAI-1 release during a 24 hour incubation). This effect was associated with a twofold increase in DNA synthesis measured by 3H-thymidine incorporation. Zymographic analysis and reverse fibrin autography showed that thrombin also increased the level of the 110 Kd t-PA-PAI-1 complex, whereas PAI-1 was present as a free 50 Kd form in the culture medium conditioned by unstimulated and thrombin-stimulated cells. Free t-PA was never observed. Both membrane binding and catalytic activity of thrombin were required since the effects of 1 U/ml thrombin were inhibited by addition 2 U/ml hirudin, which inhibits the membrane binding and catalytic activity of thrombin, and since DFP-inactivated thrombin, which has the ability to bind but which has no enzymatic activity, did not induce t-PA or PAI-1. Gamma thrombin, which does not bind to thrombin receptor, did not increase t-PA and PAI-1 releases. The effects of thrombin were probably mediated by protein kinase C activation since H7, an inhibitor of protein kinases, inhibited significantly thrombin effects on t-PA and PAI-1 production, and since addition of an activator of protein kinase A, 8-bromocyclic AMP (100 microM), induced a significant inhibition of the thrombin effect. The effects of thrombin were also suppressed by 1.25 micrograms/ml alpha amanitin, suggesting a requirement of de novo RNA synthesis. Northern blot analysis indicated that thrombin induced an increase in the mRNA levels of t-PA and of PAI-1. We conclude that thrombin increases DNA synthesis in human mesangial cells and enhances the synthesis of both t-PA and PAI-1. The latter is released in a large excess as compared to t-PA. Hence, thrombin may have a role in provoking a localized hypofibrinolytic state and may contribute to the persistence of glomerular fibrin deposits during proliferative glomerulonephritis.

Blotting, Northern↗
PubMed1990

Dexamethasone increases preproparathyroid hormone messenger RNA in human hyperplastic parathyroid cells in vitro.

To determine if parathyroid hormone release in man is directly stimulated by glucocorticoids, dispersed human parathyroid cells from hyperplastic glands obtained from eight renal transplant recipients were studied in vitro. Dexamethasone (10(-11) to 10(-6) mol l-1) increased PTH release in a time- and dose-dependent manner. A plateau was reached at 10(-8) mol l-1 (1015 +/- 149 vs. 230 +/- 27 pg 10(-4) cells for control value, after 24 h incubation; P less than 0.0001). An interaction with a glucocorticoid receptor was suggested since 10(-6) mol l-1 RU 486 blunted the dexamethasone-induced PTH release. By Northern blot analysis, dexamethasone was found to increase the amount of preproPTH mRNA in these cells. The effect of dexamethasone was probably at the gene level since (1) 1,25 dihydroxy vitamin D3 inhibited both iPTH and preproPTH mRNA increases induced by dexamethasone and (2) alpha-amanitin (1,25 micrograms ml-1) also completely suppressed the dexamethasone-induced PTH release. Thus, for the first time, we demonstrate that dexamethasone induces an increase of PTH synthesis, probably by increasing PTH gene transcription. This effect may play an important pathogenic role in persisting hyperparathyroidism and steroid-induced bone complications in renal transplant recipients.

Amanitins↗
PubMed1990

Systemic and renal fibrinolytic activity in a patient with anticardiolipin syndrome and renal thrombotic microangiopathy.

A 24-year-old white woman with a past history of recurrent venous thromboses of the lower extremities was admitted for hypertension and renal failure. She had a chronic cutaneous ulcer on the anterior side of the left leg and oral ulcers of the palatum. Laboratory tests demonstrated rapidly progressive renal failure and the presence of an anticardiolipin antibody (ELISA). Thrombosis of the inferior vena cava was shown by phlebocavography. Renal biopsy revealed typical thrombotic microangiopathy. Tissue-type plasminogen activator (tPA) was visualized by immunofluorescence in endothelial cells of renal arterioles and glomeruli. Normal plasma levels of tPA, urokinase and plasminogen activator inhibitor 1 were found by ELISA, and tPA antigen levels rose after desmopressin acetate infusion. Thus, in this case, the diffuse thrombotic process was not related to defective circulating or renal fibrinolytic systems and could be promoted by the procoagulant effect of antiphospholipid antibodies.

Adult↗
PubMed1990

Plasminogen activator inhibitor 1 in renal fibrin deposits of human nephropathies.

The persistency of fibrin deposits in the kidney during renal diseases could reflect either a defective release of plasminogen activators (PA) or a local excess of PAI. In order to investigate this question, we studied human renal biopsies by immunofluorescence technique with specific antibodies for fibrin, tissue-type plasminogen activator (t-PA), urokinase (u-PA), PAI-1 and PAI-2. By this technique t-PA could be detected in the glomerular flocculus and the endothelium of small arteries of the normal control kidneys. We failed to detect significant fluorescence with other antibodies in normal kidneys. Conversely, in cases of vascular nephropathy with thrombosis the positive fluorescence obtained with anti-fibrin antibodies at the site of thrombosis was associated with a positive fluorescence with anti-PAI-1 and to a lesser extent with anti-t-PA antibodies. u-PA and PAI-2 were not detected in these lesions. Similarly in the most severe forms of crescentic glomerulonephritis, extracapillary fibrin deposits were associated with PAI-1. In one case u-PA was also detected. This is in agreement with our previous findings that glomerular epithelial cells release both PAI-1 and the inactive form of u-PA (pro u-PA). Thus, our results support the hypothesis that PAI-1, which is able to inhibit both t-PA and u-PA, may play a major role in the persistency of fibrin deposits in the human kidneys during pathological conditions.

Female↗
PubMed1990

Fibrin deposition and adaptive changes in glomerular procoagulant and fibrinolytic activities in rat renoprival nephropathy.

To investigate the mechanisms which may influence fibrin deposition in the remnant kidney, glomerular morphology and the haemostatic properties of isolated glomeruli were assessed in two groups of rats, 30 days after surgical removal of three-quarters of the total renal parenchyma, and compared to glomeruli in sham-operated controls. One group was given the thromboxane synthetase inhibitor OKY 046 and the other was not. Fibrin deposition occurred in about 20% of glomeruli, of which 4% exhibited segmental necrotizing lesions. Concomitantly, glomerular procoagulant activity dropped to 40% of the control level and glomerular fibrinolytic activity rose to 120-130% of this level. Inhibition of thromboxane synthesis did not affect fibrin deposition, glomerular haemostasis or the development of renal insufficiency. In an additional group of unilaterally nephrectomized rats, procoagulant activity also markedly decreased in the remaining kidney. These results indicate that in the rat remnant kidney, alterations in glomerular haemostatic properties tend to have antithrombotic effects which seem to constitute an adaptive reaction by an autacoid system to glomerular fibrin deposition.

Adaptation, Physiological↗
PubMed1989

Urokinase synthesis and binding by glomerular epithelial cells in culture.

Fibrin deposits are frequently observed in the course of proliferative extracapillary glomerulonephritis and could be related to a defective local fibrinolysis. We studied human glomerular epithelial cells in culture which were found to release mainly a urokinase-type plasminogen activator (u-PA) identified on zymography by its molecular weight (53 kD), its plasminogen activator activity, and its neutralization by specific polyclonal anti-u-PA IgG. Trace amounts of tissue-type plasminogen activator (t-PA) complexed to a plasminogen activator inhibitor type 1 (PAI-1) were identified with specific antibodies. Specific binding sites were found at the surface of glomerular epithelial cells (kD: 2.10(-9) M), partially occupied by secreted u-PA. The spontaneous u-PA activity of the culture medium conditioned by glomerular epithelial cells was very low, suggesting that u-PA was released in its inactive single chain proenzyme form (SC-u-PA). After activation of SC-u-PA by plasmin, u-PA activity of the culture medium was found to increase in a time- and dose-dependent manner when cells were incubated with phorbol myristic acetate (PMA). This effect was inhibited by H7, a protein kinase C inhibitor. Stimulation of u-PA synthesis by PMA was also observed in two different epithelial tubular cell lines. LLC-PK1 and MDCK cells. However, 8 bromo cyclic AMP which increased u-PA release by LLC-PK1 cells was found to inhibit u-PA release by PMA-stimulated glomerular epithelial cells and MDCK cells. By Northern blot analysis we found that PMA induced an increase of u-PA mRNA level in glomerular epithelial cells and that cyclic AMP had an opposite effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗
PubMed1989

Characterization of a plasminogen activator and its inhibitor in human mesangial cells.

In the course of some pathological and experimental nephropathies, intraglomerular fibrin deposits develop, possibly as a consequence of inefficient fibrinolysis. In vitro human glomeruli exhibit fibrinolytic activity due to the synthesis of plasminogen activators (PAs) such as, tissue-type PA (t-PA) and urokinase-type PA (u-PA). Immunofluorescence studies have previously shown that t-PA is localized in the capillary tufts and u-PA in the visceral epithelial cells. We have now investigated the fibrinolytic activity of cultured human mesangial cells. Inhibitory activity towards u-PA or t-PA but not plasmin was found in both conditioned medium and cellular extracts. Analysis of the conditioned medium by zymography revealed a single band of PA-activity (Mr: 110 to 120 kDa). Immunoneutralization with anti-t-PA and anti-plasminogen activator inhibitor (PAI-1) IgG but not anti-u-PA or anti-PAI-2 removed this band. Reverse fibrin autography demonstrated the presence of PAI-1 in both cellular extracts and in conditioned medium. Western Blot analysis showed that two bands (50 kD and 120 kD) were recognized by the anti-PAI-1 antibody. By ELISA t-PA and PAI-1 antigens were found to increase progressively with time in the culture medium but not in cellular extracts. Both t-PA and PAI-1, but not u-PA and PAI-2, were also detected by immunofluorescence studies. Thus human glomerular mesangial cells synthesize and secrete t-PA and PAI-1 in vitro. PAI-1 is produced in excess, therefore t-PA is only found in the form of a complex with PAI-1.

Electrophoresis, Polyacrylamide Gel↗
PubMed1989

Role of the renin-angiotensin system in the regulation of glomerular filtration.

Angiotensin II (Ang II) controls renal plasma flow, which depends on perfusion pressure and on renal vascular resistances; the glomerular filtration rate of single nephrons (SNGFR) also depends on these two parameters. The glomerulus can synthesize all components of the renin-angiotensin system. Renin is produced by mesangial cells and cells of afferent arterioles, angiotensinogen by mesangial cells, and angiotensin I-converting enzyme (ACE) by endothelial and mesangial cells. Ang II binds to afferent and efferent arterioles and to mesangial cells, which subsequently contract and enhance their production of vasodilator prostaglandins. Ang II participates in the regulation of the SNGFR by acting on arteriolar resistance, on the glomerular capillary surface area, and finally on the ultrafiltration coefficient. The synthesis of renin is initiated when the cAMP concentration increases under the influence of hormones (parathyroid hormone, catecholamines), of mediators (e.g., prostanoids), or of changes in composition of tubular fluid (in sodium, chlorine, or calcium) detected by the macula densa. Moreover, renin synthesis is stimulated by decreases in intracellular calcium concentration. The renin-angiotensin system plays an important role in the regulation of glomerular filtration. A decrease in renal plasma flow is followed by an increase in glomerular efferent arteriole resistance, so that perfusion pressure and glomerular filtration remain constant. Furthermore, if the decrease in renal plasma flow is more marked, vasodilator prostaglandins, whose synthesis is stimulated by Ang II, dilate afferent arterioles, which sustains glomerular filtration. Prostaglandins are also apt to bind to the juxtaglomerular apparatus and to increase the intracellular cAMP level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗