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P Corvol

Publications and source records attributed to P Corvol.

At least 217 records · Page 12Linked to original sources
PubMed1992

[Left ventricular involvement in Conn adenoma, renovascular hypertension and pheochromocytoma before and after etiological treatment].

AIM OF THE STUDY: Assessment of left ventricular (LV) structural modifications following etiologic treatment of secondary hypertension, in a group of 43 patients. PATIENTS AND METHODS: M-Mode echocardiograms were independently analysed by 2 trained investigators before and 7.4 months (RV), 11 patients with COnn's adenoma (C) and 9 patients with phaeochromocytoma (PH). RESULTS: Age, sex ratio, antihypertensive treatment, and duration of hypertension before treatment were comparable among the 3 groups. Blood pressure was higher in C and RV than in PH for casual (C: 190/116; RV: 193/109; PH: 146/91; p < 0.01/0.05) as well as ambulatory blood pressure (C: 140/93; RV 153/89; PH: 126/80; p < 0.01/0.05). Before etiologic treatment, systolic function was normal in the 3 groups whereas LV mass index differed between the 3 groups (C: 147; RV: 118; PH: 85 g/m2). LV end diastolic diameter index was smaller in PH (26.4 mm/m2) than in C (29.1) and RV (28.8). After treatment, there was a significant reduction on office (C: -43/-20; RV: -39/-19; PH: -20/-12 mmHg) and ambulatory (C: -6.6/-5.6; R: -20/-9.9; PH: -4.7/- 4.5) blood pressure. Systolic function was not altered. LV mass index was significantly reduced in C and RV but not in PH (C: -18%; RV: -7%; PH: -5%). Changes in LV end diastolic diameter index were not significant (C: -2%; RV: 0%; PH: + 6%). There was no correlation between LV mass index changes and blood pressure differences. CONCLUSION: Etiologic treatment leads to significant regression of LV hypertrophy in patient with renovascular hypertension or Conn's adenoma, at least partly independently of blood pressure change. Humoral and volume factors may play a role in LV regression.

Adrenal Gland Neoplasms↗
PubMed1992

[Is angiotensin II a growth factor?].

Angiotensin II is an octapeptide resulting from the enzymatic cascade of the renin-angiotensin system and involved in vasoconstriction and aldosterone secretion. The extensive use of converting enzyme inhibitors recently suggested that angiotensin II may have a specific action on growth of its target tissues. Cellular models confirm that angiotensin II is able to produce in vitro a cellular hypertrophy of many cell types. Nevertheless a controversy was developed on the real possibility for angiotensin II to act on cell division. Some cells, such as adrenocortical cells, present a clear induction of their division by angiotensin II, but contradictory results were obtained on vascular smooth muscle cells. The mechanism by which angiotensin II induces hypertrophy of its target tissues, is largely unknown but may involve a direct action on proto-oncogene synthesis, or an indirect action on growth factor secretion. The nature of the angiotensin II receptor involved in these mechanisms has to be identified.

Angiotensin II↗
PubMed1991

Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene.

Overlapping genomic clones containing the entire sequence of the human angiotensin I-converting enzyme (ACE) gene were isolated from a lamda phage human DNA library. This gene spans 21 kilobases (kb) and comprises 26 exons, ranging in size from 88 to 481 base pairs. Intron-exon boundaries were sequenced and the relative positions of the exons were mapped. The two different mRNAs transcribed from the ACE gene were assigned to their respective exons. The large endothelial type ACE mRNA (4.3 kb long) is transcribed from exon 1 to exon 26, excluding exon 13. The 3-kb long testicular ACE mRNA is transcribed from exon 13 to exon 26. Exon 13 encodes for the 67 amino acids of the NH2-terminal region of the testicular ACE, whereas downstream exons encode a sequence common to both isozymes. The gene duplication suggested by the internal homology of the endothelial ACE mRNA is now confirmed by the presence of two homologous clusters of eight exons (exons 4-11 and exons 17-24) having similar sizes and codon phases at exon-intron boundaries. The presence of two alternate promoters was investigated by ribonuclease protection assays. The different 5' ends of the two ACE transcripts revealed a promoter for the endothelial ACE mRNA in the 5'-flanking region of the first exon and a promoter for the testicular ACE mRNA situated in intron 12.

Bacteriophage lambda↗
PubMed1991

The two homologous domains of human angiotensin I-converting enzyme are both catalytically active.

Molecular cloning of human endothelial angiotensin I-converting enzyme (kininase II; EC 3.4.15.1) (ACE) has recently shown that the enzyme contains two large homologous domains (called here the N and C domains), each bearing a putative active site, identified by sequence comparisons with the active sites of other zinc metallopeptidases. However, the previous experiments with zinc or competitive ACE inhibitors suggested a single active site in ACE. To establish whether both domains of ACE are enzymatically active, a series of ACE mutants, each containing only one intact domain, were constructed by deletion or point mutations of putative critical residues of the other domain, and expressed in heterologous Chinese hamster ovary cells. Both domains are enzymatically active and cleave the C-terminal dipeptide of hippuryl-His-Leu or angiotensin I. Moreover, both domains have an absolute zinc requirement for activity, are activated by chloride and are sensitive to competitive ACE inhibitors, and appear to function independently. However, the two domains display different catalytic constants and different patterns of chloride activation. At high chloride concentrations, the C domain hydrolyzes the two substrates tested faster than does the N domain. His-361,365 and His-959,963 are established as essential residues in the N and C domains, respectively, most likely involved in zinc binding, and Glu-362 in the N domain and Glu-960 in the C domain are essential catalytic residues. These observations provide strong evidence that ACE possesses two independent catalytic domains and suggest that they may have different functions.

Amino Acid Sequence↗
PubMed1991

Expression and characterization of recombinant human angiotensin I-converting enzyme. Evidence for a C-terminal transmembrane anchor and for a proteolytic processing of the secreted recombinant and plasma enzymes.

Chinese hamster ovary (CHO) cells have been transfected with either a full-length cDNA encoding human angiotensin I-converting enzyme (kininase II; EC 3.4.15.1) (ACE) or a mutated cDNA, in which the last C-terminal 47 amino acids, including the putative transmembrane domain, are not translated. Cell lines expressing high levels of the wild-type ACE or the mutant were established. The cells transfected with the wild-type cDNA (CHO-ACE) express a membrane-bound ectoenzyme with an intracellular C terminus, as shown by indirect immunofluorescence using an antiserum (28A7) raised against a synthetic peptide corresponding to the deduced C terminus of ACE. This enzyme is structurally, immunologically, and enzymatically identical to human kidney ACE. In addition, CHO-ACE cells also produce a secreted form of the enzyme. Neither this secreted form nor the enzyme purified from human plasma is recognized by the antiserum 28A7, indicating that they undergo a truncation in the C-terminal region. On the other hand, the transfected cells expressing the C-terminally truncated mutant (CHO-ACE delta COOH) do not retain ACE in the plasma membrane, but secrete it into the medium. These results indicate that ACE is anchored to the plasma membrane by the predicted C-terminal transmembrane domain, and the secreted form is derived from the membrane-bound form by a post-translational proteolytic cleavage of the C-terminal region.

Amino Acid Sequence↗
PubMed1991

Immunocytochemical localization of albumin, transferrin, angiotensinogen and kininogens during the initial stages of the rat liver differentiation.

Rat albumin, transferrin, angiotensinogen, T kininogen (TKg) and high molecular weight kininogen (HKg) gene expression was examined immunocytochemically in embryonic and fetal livers. All these plasmatic proteins, angiotensinogen excepted, are detected as early as day 11 of gestation in intestine epithelial cells and embryonic hepatocytes. Angiotensinogen becomes expressible only at day 13 of gestation. During the early fetal period, the protein immunostaining increases strikingly in parallel with the hepatocyte differentiation. Albumin and transferrin are highly expressed comparatively to kininogens and angiotensinogen. For the first time, specific HKg is demonstrated in the rat liver.

Albumins↗
PubMed1991

The kallikrein-kinin system in the rat hypothalamus. Immunohistochemical localization of high molecular weight kininogen and T kininogen in different neuronal systems.

High molecular weight kininogen (HKg) and T kininogen (TKg) were detected and localized by immunocytochemistry in adult rat hypothalamus. In addition, kininogens were measured by their direct radioimmunoassay (RIA) or by indirect estimation of kinins released after trypsin hydrolysis and high pressure liquid chromatography (HPLC) separation of bradykinin (BK) and T kinin. A specific HKg immunoreactivity demonstrated with antibodies directed against the light chain (LC) of HKg was colocated with SRIF in neurons of hypothalamic periventricular area (PVA) projecting to external zone (ZE) of median eminence (ME). Heavy chain (HC) immunoreactivity which could be related to HKg or to low molecular weight kininogen (LKg) was detected in some other systems: i) parvocellular neurons of suprachiasmatic (SCN) and arcuate nuclei containing SRIF, ii) magnocellular neurons (mostly oxytocinergic) of paraventricular (PVN) and supraoptic (SON) nuclei, iii) neurons of dorsomedian and lateral hypothalamic areas. TKg immunostaining was restricted to magnocellular neurons of PVN, SON, accessory nuclei (mostly vasopressinergic) and to parvocellular neurons of SCN (vasopressinergic). TKg projections are directed towards the internal zone (ZI) of ME, but very few immunoreactive terminals are detectable in neurohypophysis. TKg staining parallels with vasopressin during water deprivation, and is undetectable in homozygous Brattleboro rats. In some magnocellular neurons, TKg and HC (related to HKg or LKg) are coexpressed. TKg, was also detected in hypothalamus and cerebellum extracts by direct RIA, and BK and T kinin were identified after trypsin hydrolysis. HKg and LKg can act as precursor of BK which can play a physiological role as releasing factor, neuromodulator--neurotransmitter,--or modulator of local microcirculation in hypothalamus. The three kininogens are also potent thiolprotease inhibitors which could modulate both the maturation processes of peptidic hormones and their inactivation and catabolism.

Animals↗
PubMed1991

Thyroid hormone receptors and stimulation of angiotensinogen production in HepG2 cells.

Binding characteristics and effects of 3,5,-3'-triiodo-L-thyronine (T3) on angiotensinogen production in HepG2 were studied in serum-free medium. Binding was performed on intact cells and on partially purified isolated nuclei using [125I]T3. Scatchard plots revealed one class of high affinity binding sites with a Kd of approximately 80 pmol/liter. Calculation of maximum binding showed that HepG2 possess approximately 1000 binding sites per cell. Unlabeled T3 and T4 competed for binding sites on intact HepG2 with 50% inhibition of [125I] T3 binding at approximately 3.0 and 38.0 pmol/liter, respectively. The HepG2 showed a dose-dependent increase in angiotensinogen production in serum-free medium which was maximal at 10(-5) mol/liter (two-fold increase/10(6) cells/24 h) and had an EC50 of approximately 5.0 x 10(-8) mol/liter. T3 also produced after 24 h a dose-dependent increase in DNA highly correlated with T3 applied (r = 0.88, P less than 0.01). In conclusion, this study shows that HepG2 possess specific high affinity binding sites for T3 and that T3 stimulates angiotensinogen production and DNA synthesis in these cells.

Angiotensinogen↗
PubMed1991

Low angiotensinogen levels are related to the severity and liver dysfunction of congestive heart failure: implications for renin measurements.

PURPOSE: To compare the determination of plasma renin activity (PRA) and the direct measurement of active renin by immunoradiometric assay (IRMA) as methods of assessing the renin system in patients with congestive heart failure. PATIENTS AND METHODS: The status of the renin-angiotensin system in congestive heart failure was assessed by measuring the plasma renin substrate concentration, PRA, and plasma concentration of active renin in 37 patients with mild to severe congestive heart failure. Natremia and plasma levels of atrial natriuretic factor (ANF) were determined as biologic indexes of the severity of heart failure, and concentrations of prealbumin and retinol-binding protein were used as indexes of liver dysfunction. RESULTS: The PRA and the concentrations of active renin and ANF were markedly higher in patients with New York Heart Association class IV heart failure than in patients with class II to III heart failure, while natremia and the concentrations of renin substrate, prealbumin, and retinol-binding protein were markedly lower in the class IV patients than in the class II to III patients. Plasma renin substrate concentration was negatively correlated with active renin concentration (n = 37, r = -0.45, p = 0.005), and positively related to natremia (r = 0.56, p less than 0.0005), prealbumin (r = 0.54, p less than 0.001), and retinol-binding protein (r = 0.60, p less than 0.0001). CONCLUSIONS: Low levels of plasma renin substrate can be considered as an indirect index of the severity of heart failure that reflects both the high level of circulating active renin and the decrease in hepatic protein output. In patients with class IV heart failure, low levels of renin substrate led to a marked underestimation of active renin concentration from measurements of PRA. In contrast, direct IRMA of active renin measures the true plasma active renin concentration, independent of plasma renin substrate, and closely reflects renin secretion.

Adult↗
PubMed1991

Are angiotensin converting enzyme inhibition and aldosterone antagonism equivalent in hypertensive patients over fifty?

The effects of inhibiting angiotensin converting enzyme with perindopril and aldosterone with spironolactone were tested in hypertensive patients over fifty. Accordingly, 75 patients with mild hypertension aged 50 to 70 were randomly divided into three groups for a double-blind 8 week comparison of the actions of placebo, 4 to 8 mg/day perindopril, and 37.5 to 75 mg/day spironolactone. Side-effects caused one patient to withdraw from placebo and one from spironolactone treatment. Mean blood pressure rose by 2.4 mm Hg after placebo but dropped by 7.4 and 8.6 after perindopril and spironolactone (P less than .01). Placebo, perindopril, and spironolactone did not alter blood glucose or plasma potassium, but induced, respectively, variations of -0.09, 0, and +0.34 mmol/L in cholesterol (P = .04), and -0.02, -0.05, and +0.27 mmol/L in triglycerides (P less than .01). After the three treatments, changes in angiotensin converting enzyme activity averaged -1, -6, and -1 mU/mL (P less than .01), in active renin -2, +18, and +28 pg/mL (P less than .01), and in aldosterone, +15, +8, and +95 pg/mL (P less than .01). Placebo, perindopril, and spironolactone did not alter microalbuminuria, but reduced urinary kallikrein activity by 0.9, 1.8, and 5.4 mU/mmol creatinine (P = .04). Although short-term administration of spironolactone raised renin and aldosterone markedly and lipids moderately (possibly because of volume contraction), the present results show that perindopril and spironolactone are both safe and effective for treating hypertension at the age of 50 or older.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Monoclonal antibodies against a human juxtaglomerular epithelioid granular cell tumour.

With the exception of the renin-angiotensin system, the molecular composition of juxtaglomerular epithelioid granular cells (JEG cells) is unknown. We demonstrate the molecular peculiarities of these modified smooth muscle cells using monoclonal antibodies produced against a benign human JEG-cell tumour. Six out of 29 different clones produced antibodies that label JEG cells nearly exclusively. Antibodies from the other clones recognize JEG cells but also granularly or homogeneously distributed antigens of proximal tubule cells. This suggests antigenic similarity between granules of JEG cells and lysosomes of proximal tubule cells. Other clones produce antibodies which tag different cytoplasmic membranes or even mast cells. The antibodies directed exclusively against JEG cells promise to be useful tools to study their physiology and pathology.

Animals↗
PubMed1991

Cloning and functional characterization of a novel mas-related gene, modulating intracellular angiotensin II actions.

The mas oncogene codes for a GTP binding protein-coupled receptor that determines a physiological response to angiotensin when expressed in Xenopus laevis oocytes or in the neuronal cell line NG115-401L. However, another gene, rat thoracic aorta gene, structurally related to mas, is devoid of any functional similarity with the angiotensin receptor(s). The relationships between the mas-related proteins and the angiotensin receptors were investigated by identifying and characterizing new members of the mas gene family. A new mas-related gene (mrg) was cloned in a human genomic library at low stringency using the mas cDNA as probe. Mrg codes for a seven-hydrophobic-segment receptor that is 35% identical to the mas product and 29% identical to the rat thoracic aorta gene product. Mrg mRNA was not detected in several rat and human adult tissues that normally express the angiotensin II (AII) receptor, and transfections of COS and CHO cells with the mrg gene did not modify the number of AII binding sites. These results indicate that mrg and the human AII receptor genes are not identical. However, injection of mrg mRNA into Xenopus oocytes markedly increased the electrophysiological response to angiotensin peptides, indicating some functional similarities with the mas product. The reduction of the response after defolliculation of the oocyte, together with the full agonist effect of Sar1IIe8AII and the partial agonist effect of Sar1Ala8AII, seem to indicate that mrg interacts with the signaling pathways of the endogenous Xenopus angiotensin receptor to potentiate the response to AII.

Amino Acid Sequence↗
PubMed1991

[Recent advances in the investigation of the renin-angiotensin and cardiac natriuretic systems in patients with chronic heart insufficiency].

The renin-angiotensin and cardiac natriuretic systems were studied by measuring plasma renin activity, plasma concentrations of active renin, angiotensinogen, atrial natriuretic hormone and urinary cyclic GMP in 37 patients with moderate to severe cardiac failure. The plasma sodium and osmolality were chosen as markers of hydroelectrolytic imbalance and plasma concentrations of préalbumin and retinol-binding protein as indicators of the degree of hepatocellular dysfunction. Plasma renin activity (PRA) plasma concentration of active renin, atrial natriuretic hormone and urinary cyclic GMP were higher in patients in NYHA Class IV than in those in Classes II-III, whilst plasma sodium, angiotensinogen, prealbumin and retinol-binding protein concentrations were lower in Class IV patients than in patients in Classes II-III. The plasma angiotensinogen concentrations were negatively correlated with PRA (r = -0.41, p less than 0.02), active renin (r = -0.45, p = 0.005), the atrial natriuretic factor (r = -0.36, p less than 0.05) and positively correlated with prealbumin (r = 0.54, p less than 0.001) and retinol-binding protein (r = 0.60, p less than 0.0001). In NYHA Class IV patients the decreased circulating renin substrate led to an underestimation of plasma concentrations of active renin by measurement of PRA. On the other hand, direct radio-immunometric measurement of active renin allows true estimation of circulating active renin, independently of plasma angiotensinogen concentrations and thereby reliably reflects activation of the renin system. The serum sodium was negatively correlated with active renin (r = -0.66, p less than 0.0001) in these patients not receiving converting enzyme inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Distribution of plasma angiotensin I-converting enzyme levels in healthy men: relationship to environmental and hormonal parameters.

Angiotensin I-converting enzyme (ACE) levels in plasma are stable in a given individual but differ greatly among subjects. To establish the distribution of plasma ACE levels and the mechanisms that are involved in the interindividual variability in this enzyme, plasma ACE has been determined by direct radioimmunoassay in a group of 434 healthy, middle-aged, Caucasian men and compared with several hemodynamic, environmental, and hormonal parameters. The distribution of ACE is assymetric. The interindividual variability is large since ACE levels can differ up to 5.7 times among subjects. No association, however, was observed with candidate environmental or hormonal parameters to explain the interindividual variability in plasma ACE levels. A weak association was observed between ACE and blood pressure. A previous study, conducted in nuclear families, has shown that differences among subjects in plasma ACE levels are, in part, genetically determined. The present study does not reveal other determinants, either hormonal or environmental, of the interindividual variability in this enzyme. The characteristics of the distribution of plasma ACE levels should be considered when a value is interpreted in a given patient.

Analysis of Variance↗
PubMed1991

[Use of intravenous nicardipine for the diagnosis of renovascular hypertension].

UNLABELLED: The diagnosis of remediable renovascular hypertension (RVH) requires demonstration of lateralization of renal vein renin (RVR). In order to increase the accuracy of RVR ratio, we investigated the acute effects of a bolus of Nicardipine (Nic.: 4 mg i.v.) on hemodynamics and RVR in 19 patients. 13 patients had an unilateral renal artery stenosis greater than 75% (RVH: 10 atheroma and 3 fibrodysplasia) and 6 patients had essential hypertension (EH). In 6 patients (5 RVH and 1 EH) treatment could not be discontinued and only a monotherapy by central alpha-agonists was prescribed. RVR samples were obtained 15 minutes after renal vein catheterization (baseline values: T0) and 10 minutes after Nic. injection (T10). During the whole procedure, mean blood pressure (MBP) and heart rate (HR) were monitored every 2 minutes by an automatic device. Active renin was measured by a new immunoradiometric assay. A RVR ratio (stenotic/contralateral side) greater than 1.5 was considered as a positive ischemic index. RESULTS: The relative changes in MBP and HR between T0 and T10 were of same magnitude in both groups. No patient suffered any untoward effect from the fall in MBP. Nic. increased RVR release from both sides in RVH group as well as in the EH group. At baseline, 6/13 of the RVH patients and none of the EH patients had a RVR greater than 1.5. After Nic. injection, all the RVH patients had a RVR greater than 1.5 and none among EH patients. We conclude that single i.v. Nic. bolus is a safe and a reliable procedure which increases diagnostic accuracy by enhancing RVR when there is an unilateral RVH disease.

Adult↗