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Biomedical subjects

P Corvol

Publications and source records attributed to P Corvol.

At least 253 records · Page 14Linked to original sources
PubMed1990

Stimulation by hCG of ovarian inactive renin synthesis in rabbit preovulatory theca cells.

The origin of ovarian renin and its regulation by hCG were investigated in rabbit periovulatory follicles and cultured preovulatory follicular cells. Intracellular content of renin in thecal cells was 8-fold greater than of granulosa cells. In vivo, administration of hCG increased intracellular content of renin in thecal but not granulosa cells. Similar results were obtained for cultured follicular cells, from which renin was partly released into the medium. In vitro, hCG increased intracellular renin content of thecal but not granulosa cells, without obvious effect on release. Approximately 95% of ovarian renin was inactive, but could be activated by trypsin. Thecal renin was antagonized in vitro by renin antiserum, indicating a specific renin activity. Our study establishes in the rabbit the thecal cell origin of ovarian inactive renin and demonstrates hCG regulation of its synthesis.

Animals↗
PubMed1990

The angiotensin I-converting enzyme (kininase II): progress in molecular and genetic structure.

The complete amino acid sequence of the human angiotensin I-converting enzyme (ACE) has been determined by protein sequencing of the purified kidney enzyme and cDNA cloning in endothelial cell libraries. The ACE molecule comprises 1,306 amino acids. It possesses a signal peptide of 29 residues cleaved off during maturation. The enzyme is most likely anchored to the plasma membrane by a short transmembrane domain situated near the carboxy-terminal extremity. Interestingly, the molecule presents a high degree of internal homology between two large peptidic domains. Each of these domains contains short sequences identical to zinc binding and active site sequences of other zinc metallopeptidases and therefore bears a putative active site. However, earlier experiments indicate only one zinc atom bound per molecule of ACE. Competitive inhibitors seem to interact with a unique class of high-affinity binding site. These observations may suggest that, despite the duplicated structure of the enzyme, there is only one functional active site per molecule of ACE. The respective role of the two homologous domains in this active site remains to be determined. A single gene coding for ACE is present in humans, transcribed as a 4.3-kilobase mRNA species in endothelial cells. In other studies, evidence for a genetic polymorphism in plasma ACE levels has been obtained by analyzing a large group of "healthy" nuclear families. A familial association of plasma ACE levels was observed. A major gene effect can possibly explain part of the interindividual variability observed in this enzyme.

Amino Acid Sequence↗
PubMed1990

Successful detection by in situ cDNA hybridization of three members of the serpin family: angiotensinogen, alpha 1 protease inhibitor, and antithrombin III in human hepatocytes.

In situ hybridization was used to investigate the presence of mRNAs of three members of the serine protease inhibitor (serpin) superfamily, angiotensinogen (AG), alpha 1 protease inhibitor (alpha 1PI), and antithrombin III (ATIII) in normal human liver. The probes were full length 35S radiolabeled complementary DNAs of human AG, alpha 1PI, and ATIII. The three mRNAs were found to be uniformly distributed in all hepatocytes, with no evidence of any special distribution, but the signal was more intense for alpha 1PI than for AG and ATIII. Kupffer cells, biliary epithelial cells, and vascular cells were all negative. The same tissue was studied by peroxidase-antiperoxidase immunohistochemistry using specific antibodies against AG, alpha 1PI, and ATIII. No significant amounts of any of the proteins, alpha 1PI, AG, or ATIII were detected in frozen or fixed sections of normal liver. This study indicates that these proteins are not stored in the normal human hepatocyte, but that their genes are actively expressed and that in situ hybridization is the only technique presently available to detect their presence.

Angiotensinogen↗
PubMed1990

[18-Hydroxycorticosterone, 18-hydroxydesoxycorticosterone. Why, when, how to determine plasma levels in some adrenal pathologies].

The authors review some current ideas concerning the role of 18-hydroxylated corticosteroids as mineralocorticoids themselves and as possible precursors of the principal mineralocorticoid, aldosterone. In particular, the physiological and pharmacological agents affecting their secretion are discussed together with a description of the methods used for their analysis in plasma in the department of Clinical Biochemistry Pitié-Salpétrière. Finally, the value of these assays in the differential diagnosis of mineralocorticoid hypertension and inborn errors of corticosteroid biosynthesis is assessed and the constraints on sampling technique listed.

18-Hydroxycorticosterone↗
PubMed1989

Evidence for a single active site in the human angiotensin I-converting enzyme from inhibitor binding studies with [3H] RU 44 403: role of chloride.

Binding of the potent radiolabelled competitive inhibitor 3H RU 44403 to pure human kidney angiotensin-I converting enzyme was examined in equilibrium and non equilibrium conditions. Equilibrium dialysis experiments indicate that, despite the duplicated structure of the enzyme and the presence of two putative active sites, 3H RU 44403 interacts with a single high affinity (Kd = 0.44 +/- 0.05 x 10-9 M, n = 3) binding site. This suggests that only one of the two putative active sites is functional, and can bind substrates or inhibitors. Sodium chloride plays an essential role in the enzyme-inhibitor interaction. The formation of the complex is only slightly influenced by NaCl, but the kinetic of dissociation is dramatically dependent on NaCl concentration. In a Nacl free medium the complex is unstable and dissociates rapidly. These results are consistent with the hypothesis that chloride ion influences isomerization of the complex toward a more stable form.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

The testicular transcript of the angiotensin I-converting enzyme encodes for the ancestral, non-duplicated form of the enzyme.

The endothelial angiotensin I-converting enzyme (ACE) is organized in two large homologous domains, each bearing a putative active site. However, only one of these sites is probably involved in catalyzing the conversion of angiotensin I into angiotensin II. The testicular form of ACE is equally active, encoded by the same gene, but translated from a shorter mRNA. Molecular cloning of the human testicular ACE cDNA indicates that the mRNA codes for 732 residues (vs 1306 in endothelium). The testicular transcript corresponds to the 3' half of the endothelial transcript and encodes one of the two homologous domains of endothelial ACE, preceded by a short specific sequence. This 5' specific sequence contains 228 nucleotides and encodes 67 amino acids, including the putative signal peptide followed by a serine/threonine-enriched region, presumably glycosylated. The testicular transcript corresponds to the ancestral, non-duplicated form of the ACE gene. Since the carboxyl-terminal domain of the endothelial ACE is expressed in the testicular enzyme, it is likely that it bears the active site in both forms.

Amino Acid Sequence↗
PubMed1989

[Recent advances in the clinical study of the renin system. Reference values and conditions of validity].

Plasma renin activity, angiotensinogen, active renin and aldosterone concentrations and, 1 hour after addition of trypsin 1 mg per ml of plasma at -4 degrees C, prorenin and total renin concentrations were measured in 49 normotensive volunteers. Renin activity and active renin concentration were correlated (n = 98, r = 0.902, p less than 0.01) and their ratio was not dependent on the angiotensinogen concentration. Prorenin accounted for 90 per cent of total renin and was 40 per cent higher in males than in females in both supine and upright positions (p = 0.02 and p = 0.01). The change in position markedly increased plasma renin activity as well as active renin and aldosterone concentrations and, to a lesser degree, prorenin concentration, thereby raising the active/total renin ratio. Plasma renin activity, active renin concentration and plasma aldosterone concentration were significantly and negatively correlated with age, but not with urinary sodium excretion. Plasma renin activity and active renin and angiotensinogen concentrations were also measured in 14 patients with high angiotensinogen concentration (pregnant women and oestrogen users) and in 14 patients with cirrhosis and subnormal angiotensinogen concentration. In these patients the ratio of plasma renin activity to active renin concentration was correlated with the angiotensinogen concentration (n = 28, r = 0.643, p less than 0.01). The slope of the regression line between renin activity and active renin concentration was significantly different in patients with cirrhosis and in healthy volunteers, the measurement of renin activity leading to a ten-fold underestimation of active renin concentration. In clinical investigations of the renin system, plasma samples should be handled at room temperature to avoid cryoactivation of prorenin. The determination of active renin concentration should be preferred to that of plasma renin activity because it is not influenced by physiological or pathological variations in angiotensinogen.

Adolescent↗
PubMed1989

Renin and cathepsin B in human pituitary lactotroph cells. An ultrastructural study.

Renin, prorenin and cathepsin B were localized in human lactotrophs using immunoelectron microscopic techniques. Renin and prorenin were found in numerous cytoplasmic granules. Cathepsin B, a lysosomal enzyme known to be able to activate prorenin into renin, was also present in cytoplasmic granules of lactotrophs. The co-localization of renin and prolactin in the same secretory granules was demonstrated by double immunolabelling. Renin and cathepsin B were co-localized in some granules by the same technique. These results suggest a local activation of renin in the secretory granules of lactotrophs and support the hypothesis of a possible autocrine action of the renin-angiotensin system on prolactin release.

Adenoma↗
PubMed1989

Immunologic approaches to blockade of the renin-angiotensin system: a review.

Several immunologic approaches to blockade of the renin-angiotensin system (RAS) have been reported, involving most of the proteins and peptides of the biochemical cascade: renin, substrate, angiotensins, and converting enzyme. None as yet has involved blockade of angiotensin II receptors. Earlier and more recent studies used passive transfer of heterologous antibodies or active immunization against RAS proteins and peptides. Passive transfers have been performed with both polyclonal antibodies and now with specific monoclonal immunoglobulins. The latter are better defined in affinity, quantity, and capacity to bind and thus inhibit the biologic activity of the antigen. Active immunization produced long-term blockade of part or all of the biologic activity of the system. The immunopathologic consequences of the use of antibodies raised against a self-antigen could be of interest in defining the predominant site of storage and secretion of the relevant protein and hence the respective roles of different tissues in the production of specific proteins in, for example, the vascular pulmonary bed for converting enzyme and renal arterial tree for renin. In all cases immunologic methods offer in vivo experimental models of short- or long-term RAS blockade that could be compared with pharmacologic methods, such as converting-enzyme inhibition, angiotensin II antagonists, and renin inhibitors.

Angiotensin I↗
PubMed1989

Antialdosterones: incidence and prevention of sexual side effects.

The use of spironolactone in the treatment of hypertension has been limited by the occurrence of sexual side effects, mainly menstrual disturbances in women and gynaecomastia in men. In order to minimize this limitation on the use of an effective potassium-sparing antihypertensive agent, two strategies can be proposed: (1) A decrease in the daily dose of spironolactone. In 182 patients with essential hypertension treated with spironolactone alone for a mean follow-up period of 23 months, daily doses of 75-100 mg were as effective on blood pressure as doses of 150-300 mg. In contrast, the development of gynaecomastia--91 cases among 699 men--was dose-related in 6.9% (50 mg/day) to 52.2% (150 mg or more/day) of the cases. (2) An improvement in the receptor-binding specificity of spironolactone. Three 9 alpha, 11 alpha-epoxy derivatives have been characterized in vitro in rats and in rabbits. They exhibited a 3- to 10-fold decrease of the antiandrogenic and progestagenic effect, compared with spironolactone. In humans, one of these derivatives counteracted the fall in urinary Na/K ratio induced by 9 alpha-fluorohydrocortisone at a 25 mg dose.

Blood Pressure↗
PubMed1989

Effect of sex hormones on plasma T-kininogen in the rat.

The influence of sex hormones on rat plasma T-kininogen concentration was examined. The level of T-kininogen in the post-pubertal female rat is about 3-times that of the male animal. Female rats castrated as adults or 15 days after birth, had low T-kininogen concentrations, near those of male rats. In contrast, castration of mature or immature male animals induced no change in T-kininogen. Treatment of castrated female or male rats with 17 alpha-ethinylestradiol significantly increased the T-kininogen level, whereas administration of testosterone or progesterone had no effect. The influence of estrogen was specific for T-kininogen, since plasma HMW kininogen concentration was the same in male and female rats and was not affected by castration or sex hormone treatment. T-kininogen concentration was not significantly changed in pregnant rat between the 12th and the 20th day of pregnancy, but increased after parturition. It was high in the newborn rat at birth and then decreased similarly over the next 3 weeks in males and females. It continued to decrease in the males, reaching the level of the adult rat, but it increased in the female from 3-4 weeks of age and reached the adult level at about 6-8 weeks. These data indicate that natural estrogens have a physiological influence on the plasma level of T-kininogen in female rats whereas testosterone had no effect on either male or castrated female rats. HMW kininogen is not physiologically dependent on sex hormones.

Acute-Phase Proteins↗
PubMed1989

Structure of human angiotensinogen gene.

A cDNA clone encoding human angiotensinogen was isolated from a cDNA library prepared from human liver mRNA and used to isolate the angiotensinogen gene. The complete exon sequence of this gene together with extensive intron and flanking sequences are reported. The human angiotensinogen gene contains five exons interrupted by four intervening sequences. We compared the intron-exon structure of this human gene with that of the rat gene or the genes coding for proteins such as alpha 1-antitrypsin and antithrombin III, whose primary amino acid sequences show similarities. The human angiotensinogen gene shows identical organization with the alpha 1-antitrypsin gene, but is different from the antithrombin III gene. The 5'-flanking sequence (-500 to -1 bp) of the human angiotensinogen gene was examined for hormone regulatory elements (HRE), which may be implicated in the interaction with the hormone receptor complexes.

Amino Acid Sequence↗
PubMed1989

Plasma angiotensins, renin, and blood pressure during acute renin inhibition by CGP 38 560A in hypertensive patients.

The new renin inhibitor CGP 38560A has been shown to block angiotensin (ANG) production in healthy volunteers. In order to determine its potential antihypertensive effect, the compound was administered in a 30-min infusion, in 12 hypertensive patients (mean blood pressure (BP): 112.8 +/- 3.5 mm Hg). These patients were selected for their sensitivity to captopril: a single oral dose of 50 mg captopril lowered their mean BP by 8.8 +/- 2.2 mm Hg after 30 min and by 15.3 +/- 1.5 mm Hg after 90 min. At the end of the renin inhibitor infusion, mean blood pressure decreased by 5.7 +/- 2.2 mm Hg in the six patients infused with the dose of 0.125 mg/kg and by 6.0 +/- 1.8 mm Hg in the six patients infused with 0.250 mg/kg. The fall in blood pressure was correlated to the initial plasma renin activity (PRA) (r = 0.61, P less than .05). A dose-dependent effect was observed on plasma ANG I which fell by 74% with 0.125 mg/kg and by 94% with 0.250 mg/kg. Identical falls were found for plasma ANG II (72% and 94%, respectively) and ANG I and ANG II were well correlated (r = 0.91, P less than .001). The fall in BP was correlated to the fall in plasma ANG I (r = 0.77, P less than .01). The time-course of the BP changes was parallel to the changes in plasma angiotensins, as were the slightly delayed rise and fall in active renin measured by a direct immunoradiometric assay. When measured by the conventional ANG I radioimmunoassay, PRA values indicated a long-lasting inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Regulation of angiotensinogen gene.

The development of recombinant DNA technology has introduced new directions for the study of the angiotensinogen molecule. The cloning and sequencing of the human and rat cDNAs demonstrate the similarity of angiotensinogen to various serine protease inhibitors produced by the liver and was the beginning of studies looking for new physiological roles of angiotensinogen, in addition to the substrate for renin. The determination of the nucleotide sequence of these cDNAs also allowed the identification of angiotensinogen mRNA in many tissues in addition to the liver that is the major site of synthesis. This multilocalization of angiotensinogen is one of the arguments for the presence and the function of local renin-angiotensin systems. Finally, the hepatic biosynthesis of angiotensinogen is regulated by many different hormonal factors including glucocorticoid, estrogen, thyroid hormone, insulin, and angiotensin II. The cloning of the angiotensinogen gene offers the opportunity to study this regulation at the transcriptional level. We present in this paper a review of the literature concerning the new aspects of angiotensinogen using molecular biological tools and its regulation together with the characterization of the human angiotensinogen gene.

Amino Acid Sequence↗
PubMed1989

Influence of age on the outcome of percutaneous angioplasty in atheromatous renovascular disease.

We compared the efficacy and safety of percutaneous transluminal renal angioplasty for the treatment of renovascular disease in 66 patients. Thirty-four were aged less than 60 years, and 32 more than 60 years. The younger patients had a shorter known duration of hypertension and higher levels of diastolic pressure (6.4 +/- 9 years and 109 +/- 15 mmHg) than the older patients (12.8 +/- 8 years and 101 +/- 11 mmHg, P less than 0.01 for both comparisons). They also had higher creatinine clearance rates (78 versus 46 ml/min, P less than 0.01) and less severe renal artery disease. A total of 70 percutaneous transluminal renal angioplasties were performed in 70 arteries with a technical success rate of 100% in the younger group versus 67% in the older group (P less than 0.01); complications occurred more frequently in the older group. Our data indicate that, when technically successful, percutaneous transluminal renal angioplasty improves blood pressure to a similar extent in both younger and older patients. However, in patients over 60 years, the safety of the procedure is limited by more severe age-associated atheroma of renal and extrarenal arteries.

Aging↗