[Hereditary factors of essential arterial hypertension].
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Biometry↗
Biomedical subjects
P Corvol
Publications and source records attributed to P Corvol.
[Intraluminal angioplasty in renovascular arterial hypertension. 104 cases].
Between January 1, 1985 and January 1, 1988, 104 patients with arterial hypertension and renal artery stenosis were treated by percutaneous transluminal angioplasty (PTA). The procedure was justified by the resistance of hypertension to other treatments in 50 patients with atheromatous stenosis and 38 patients with fibrodysplasic stenosis. In the remaining 16 patients, who had severe atheroma, PTA was made necessary by ischaemic renal failure. Out of 52 PTAs (including 2 bilateral in one stage) performed in atheroma patients without renal failure, 48 (92 per cent) were immediate technical successes. In 44 patients arterial pressure measurements after 7.5 months (2-24) showed cure in 6 cases (13 per cent), improvement in 29 cases (66 per cent) and failure in 9 cases (21 per cent). Control arteriography of 40 arteries showed success in 28 cases (70 per cent), residual stenosis in 9 (22 per cent) and restenosis in 3 cases (8 per cent) (2 secondary successes of PTA). In patients with fibrodysplastic stenosis, 42 PTAs (4 bilateral) resulted in immediate angiographic success in 81 per cent. In 34 patients arterial pressure measurements after 8.2 months (2-35) showed cure in 2 cases (65 per cent), improvement in 10 cases (29 percent) and failure in 2 cases. Angiography of 34 arteries showed success in 31 (91 per cent) and restenosis in 3 (2 bypasses). In 13 of the 16 patients with renal failure, the renal function was stabilized by PTA, but 5 patients needed surgery and 2 were put on chronic dialysis. It is concluded that the immediate and medium term success rates of renal angioplasty confirm the value of this recanalization procedure in fibrodysplasia and atheroma.
Adult↗
Assignment by in situ hybridization of the angiotensinogen gene to chromosome band 1q4, the same region as the human renin gene.
A 1.8 kb human cDNA probe for angiotensinogen (renin substrate) was used to determine the chromosomal location of the angiotensinogen gene by in situ hybridization. The results show that human chromosome region 1q4 contains the angiotensinogen gene. The human renin gene has also recently been assigned to the same band of chromosome 1. Thus, the angiotensinogen and renin genes are located in the same region of chromosome 1.
Angiotensinogen↗
Effects of captopril and minoxidil on left ventricular hypertrophy in resistant hypertensive patients: a 6 month double-blind comparison.
In a double-blind 6 month trial, the cardiac effects of captopril and minoxidil, administered as third step treatments, were compared in 34 men with essential hypertension and diastolic blood pressure greater than 95 mm Hg who were taking 200 mg/day of metoprolol and 80 mg/day of furosemide. Average daily doses of captopril and minoxidil were 269 mg (range 150 to 300) and 20 mg (range 7.5 to 30), respectively. At the end of the 6 months' treatment, blood pressure had dropped significantly in both groups, but echocardiographic criteria of hypertrophy improved only in the captopril group (intragroup comparison): blood pressure, thickness of the intraventricular septum and posterior wall, and the left ventricular mass index, respectively, decreased from 163/102 to 135/89 mm Hg (p less than 0.001), 17.4 to 15.9 mm (p less than 0.05), 14.5 to 13.4 mm (p less than 0.05) and 236 to 198 g/m2 (p less than 0.001). In the minoxidil group, blood pressure dropped from 160/99 to 137/87 mm Hg (p less than 0.001), but echocardiographic criteria were not significantly modified. Fractional shortening remained normal in both groups. These results show that in patients with severe left ventricular hypertrophy, captopril-based triple therapy reduces left ventricular mass without altering systolic performance, whereas minoxidil-based therapy does not.
Adult↗
Involvement of a pertussis toxin-sensitive G protein in the regulation of angiotensinogen production by an angiotensin II analog in HepG2 cells.
The cellular mechanism by which the angiotensin II (AII) agonist, Sar1-AII, inhibits production and release of angiotensinogen in human hepatoma HepG2 cells was examined. Pretreatment of HepG2 cells with pertussis toxin attenuated the ability of Sar1-AII to block angiotensinogen production. This effect could be correlated with the in situ ADP-ribosylation of a protein(s) of apparent molecular weight 39,000-41,000 on SDS-PAGE, and attenuation of the ability of Sar1-AII to inhibit cAMP accumulation. The role of cAMP in angiotensinogen production was examined. A transient increase in cAMP accumulation above basal could be evoked by forskolin (8-fold) or by glucagon (5-fold) using insulin-deficient media. Although neither forskolin nor glucagon had a significant effect on angiotensinogen production agents producing a sustained increase in intracellular cAMP (8-bromo-cAMP, dibutyryl-cAMP, cholera toxin) were able to increase angiotensinogen production. Although these data indicate that intracellular cAMP is a regulatory factor in angiotensinogen production other evidence suggests that modulation of intracellular cAMP is not entirely responsible for the effects of Sar1-AII.
Adenosine Diphosphate Ribose↗
Arginine vasopressin gene expression in chronic cardiac failure in rats.
Arginine vasopressin (AVP) is known to be increased in patients and experimental animals with chronic cardiac failure (CCF). The importance of an increase in biosynthesis of AVP in the hypothalamus has, however, not heretofore been investigated and is the purpose of the present study. CCF secondary to infarction of myocardial tissue was induced by ligation of the left anterior descending coronary artery and sham operated animals served as controls. Four weeks later hypothalamic AVP mRNA was determined by solution hybridization using sense and anti-sense strand RNA. The blood pressure was lower in CCF than sham animals (131.2 +/- 3.1 vs. 112.8 +/- 4.0 mm Hg, P less than 0.05) and the total heart, and right and left ventricle weights were significantly higher in CCF rats. Plasma AVP was higher in CCF (sham 6.78 +/- 0.30; CCF 11.46 +/- 0.64 pg/ml, P less than 0.001) and plasma atrial natriuretic peptide was also higher in CCF than sham animals (205 +/- 36 vs. 554 +/- 56 pg/ml, P less than 0.001). The AVP mRNA in hypothalamus was significantly higher in CCF than sham animals (55.5 +/- 3.7 vs. 95.9 +/- 4.0 pg/micrograms total RNA, P less than 0.001). There was no difference in beta-actin mRNA in the hypothalamus of sham and CCF rats, indicating that the AVP-mRNA increase was specific in CCF. These results therefore demonstrate that increased AVP biosynthesis in the hypothalamus, in addition to release of the hormone from the posterior pituitary, may occur in CCF.
Animals↗
Urinary cyclic guanosine monophosphate as an indicator of experimental congestive heart failure in rats.
STUDY OBJECTIVE--The aim was to investigate the relationship between urinary cyclic guanosine monophosphate (GMP) excretion and activation of the heart endocrine function in two rat models of cardiac failure. DESIGN--Left ventricular infarction and aging in spontaneously hypertensive rats (SHR) are two models that could lead to congestive heart failure. In the first the degree of failure depends on the length of the infarcted area. In the second the degree of failure depends on time. Urinary cyclic GMP, plasma atrial natriuretic factor (ANF), and degree of congestive heart failure were evaluated in both models. EXPERIMENTAL ANIMALS--31 male Wistar rats were used for myocardial infarction and sham operated controls. Spontaneously hypertensive (SHR) rats (2, 6, 12 and 24 months old, n = 10 per group) were used for the age overload studies. MEASUREMENTS AND MAIN RESULTS--In myocardial infarction, the amount of left ventricular ANF mRNA, plasma ANF concentration, and urinary cyclic GMP excretion were correlated and were proportional to the degree of cardiac failure, as assessed by the increase in right ventricular mass and the decrease in blood pressure. In male SHR (aged 6-24 months), plasma ANF and urinary cyclic GMP were correlated, increased with age, and were proportional to the heart to body weight ratio. These correlations between plasma ANF, daily urinary cyclic GMP excretion, and left ventricular hypertrophy persisted in two year old SHR. The presence of pleural extravasation in these old animals was also characterised by significant increases in both plasma ANF and urinary cyclic GMP. The plasma ANF and the daily urinary cyclic GMP excretion were negative prognostic indicators of life expectancy in two year old SHR. CONCLUSIONS--Urinary cyclic GMP excretion, correlated with the plasma ANF level, is a non-invasive indicator of congestive heart failure in two models of overloaded left ventricle in rats.
Aging↗
Clinical implications of the molecular biology of the renin-angiotensin system.
Molecular cloning of the renin-angiotensin system (RAS) genes has supplied new tools for investigation for the pharmacologist, the physiologist and the geneticist concerned with blood pressure. The main questions regarding the RAS that can be addressed by molecular biology are: (1) How can new inhibitors of the RAS be designed? Molecular cloning of renin and angiotensin-converting enzyme and production of the corresponding recombinant protein are the basis for understanding the molecular mechanism of catalysis and for identifying residues corresponding to catalytic subsites. (2) Do local RASs exist and, if so, what is their physiological importance? Cloned genes of this system represent specific probes that can be used to identify the sites of transcription and to evaluate the degree of expression of the genes by measuring the level of their mRNA. (3) Is elevation of blood pressure in essential hypertension related to an abnormality in one of the RAS genes? Cloning of the different genes has allowed the detection of polymorphism at the nucleotide level, representing inter-individual variations of the sequences of the genes.
Humans↗
Effect of bradykinin and kininogens in isolated rat kidney vasoconstricted by angiotensin II.
The hemodynamic and endocrine effects of bradykinin and kininogens were investigated using a closed-circuit isolated rat kidney perfused with angiotensin II (ANG II). ANG II induced vasoconstriction, stimulation of urinary kallikrein release, and inhibition of renin secretion. Bradykinin markedly increased renal perfusate flow (RPF) and produced a slight but significant diuresis and natriuresis. The inhibitory effect of ANG II on renin secretion was delayed. Urinary kallikrein secretion was unchanged. The effect of bradykinin was suppressed by the competitive kinin antagonist [DArg,Hyp3,Thi5,8,DPhe7]bradykinin. Kallikrein-sensitive rat high-molecular-weight kininogen produced a progressive rise in renal perfusate flow. Exocrine function and renin and kallikrein secretions were unchanged. Immunoreactive kinins, identified as bradykinin by high-pressure liquid chromatography, were liberated into the perfusate. Perfusate immunoreactive high-molecular-weight kininogen decreased in parallel as a result of consumption. The kalikrein-resistant T-kininogen was not hydrolyzed to release a kinin, had no effect on renal function, and its concentration in the perfusate remained constant. These results suggest that kinin can be produced in the renal circulation from kallikrein-sensitive circulating kininogens and can antagonize the vasoconstrictor effect of ANG II and alter renal hemodynamics. They provide evidence that the kallikrein-kinin system can participate with the renin-angiotensin system in the control of renal blood flow.
Angiotensin II↗
The difficult challenge of cloning the angiotensin II receptor.
The vasopressor peptide angiotensin II exerts its cellular effects through a membrane-bound receptor coupled to a G protein. Biochemical and pharmacological analyses of this receptor already identify two different membrane-bound receptors and one cytosoluble angiotensin-II-binding protein. Nevertheless, the purification of the membrane-bound form(s) appears to be difficult. In the absence of purified protein, two cloning strategies of the gene have been explored: (1) expression cloning, identifying the functions of the protein expressed from a cDNA library in COS cells or Xenopus oocytes, has been unsuccessful until now; (2) analogical cloning, trying to identify related members of the seven transmembrane segment receptor family, which could be related to angiotensin receptors, identifies the mas oncogene and two related genes. However, there are accumulating data to exclude their involvement in angiotensin binding.
Animals↗
Immunoradiometric assay of active renin versus determination of plasma renin activity in the clinical investigation of hypertension, congestive heart failure, and liver cirrhosis.
We compared the determination of plasma renin activity (PRA) and the direct immunoradiometric measurement of active renin (AR) as ways of assessing the activity of the renin-angiotensin system in normal volunteers and in patients with hypertension, heart failure, or liver failure. The levels of plasma renin substrate, angiotensinogen, and the ratio of PRA to AR concentration did not differ in the normal volunteers and the patients with essential or renovascular hypertension. However, compared to the volunteers, patients with severe heart or liver failure had markedly reduced plasma renin substrate levels, which led to a considerable underestimation of AR concentration when it was measured by PRA.
Adult↗
Atrial natriuretic factor as a marker in congestive heart failure.
Cardiac overload is associated with an overexpression of the atrial natriuretic-factor (ANF) gene in experimental models and in man. Sites of ANF gene overexpression are the atria but also the ventricular myocardium. This recruitment phenomenon of the ventricle to synthesise and secrete ANF is directly dependent on the increase in stress-stretch relationship in each cardiocyte. Therefore, the levels of plasma ANF and its second messenger, cyclic glycophosphate mutase in plasma and urine appear as markers of congestive heart failure in animal models and in man. Particularly, plasma ANF has been recognized recently as independent prognostic factor in congestive heart failure.
Atrial Natriuretic Factor↗
Physiological and immunopathological consequences of active immunization of spontaneously hypertensive and normotensive rats against murine renin.
Spontaneously hypertensive Okamoto-strain rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were actively immunized with mouse renin to investigate the effect on blood pressure of blocking the renin-angiotensinogen reaction. Ten male SHR and 10 male WKY rats were immunized with purified mouse submandibular gland renin. Control rats were immunized with bovine serum albumin. Antirenin antibodies were produced by both SHR and WKY rats, but renin-immunized SHR had higher titers of circulating renin antibodies after three injections. The increase in renin antibody in renin-immunized SHR was associated with a significant drop in blood pressure (tail-cuff method) that became similar to that of the WKY control rats after four injections. The blockade by antirenin immunoglobulins of the renin-angiotensinogen reaction also decreased the blood pressure of normotensive rats. Perfusion of renin-immunized rats with mouse submandibular renin (10 micrograms) in vivo caused no increase in blood pressure. Perfusion of renin-immunized, salt-depleted SHR with converting enzyme inhibitor caused no further decrease in blood pressure but significantly decreased blood pressure in salt-depleted control rats. The presence of circulating renin antibodies was associated with low plasma renin activity (0.31 +/- 0.23 ng angiotensin I [Ang I]/ml/hr). Plasma renin activity was unchanged in control animals (13.1 +/- 3.9 ng Ang I/ml/hr in control SHR, 13.9 +/- 3.2 ng Ang I/ml/hr in control WKY rats). Renin antibody-rich serum produced a dose-dependent inhibition of rat renin enzymatic activity in vitro. The chronic blockade of the renin-angiotensinogen reaction in renin-immunized SHR produced an almost-complete disappearance of Ang II (0.8 %/- 7 fmol/ml; control SHR, 30.6 +/- 15.7 fmol/ml) and a 50% reduction in urinary aldosterone. Renin immunization was never associated with a detectable loss of sodium after either 10 or 24 weeks. The glomerular filtration rate was not decreased 10 weeks after renin immunization, whereas blood pressure was significantly decreased, plasma renin activity was blocked, and renal plasma flow was increased. The ratio of left ventricular weight to body weight after 24 weeks was significantly below control levels in renin-immunized WKY rats and SHR. Histological examination of the kidney of renin-immunized SHR showed a chronic autoimmune interstitial nephritis characterized by the presence of immunoglobulins, mononuclear cell infiltration, and fibrosis around the juxtaglomerular apparatus. These experiments demonstrate that chronic specific blockade of renin decreases blood pressure in a genetic model of hypertension in which the renin-angiotensin system is not directly involved.(ABSTRACT TRUNCATED AT 400 WORDS)
Aldosterone↗
Human renin inhibitor peptides.
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Angiotensin-Converting Enzyme Inhibitors↗
Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects.
A prospective study was conducted to compare the frequency of renin gene polymorphisms in normotensive and hypertensive subjects. Hypertensive (n = 102, blood pressure 168 +/- 17/103 +/- 9 mm Hg) and normotensive (n = 120, blood pressure 122 +/- 10/75 +/- 9 mm Hg) subjects were white, had similar age and sex distributions (hypertensive group, 45 +/- 10 years old and 52% female; normotensive group, 44 +/- 9 years old and 55% female) and similar body mass index (hypertensive group, 23.2 +/- 2.6; normotensive group, 22.5 +/- 2.4 kg/m2, p = 0.048). The familial susceptibility to hypertension was defined as at least one parent and one sibling who were hypertensive before age 65; subjects in the normotensive group had no familial history of hypertension. Renin gene polymorphisms located throughout the renin gene were identified by using three restriction enzymes (Taq I, HinfI, HindIII). For each polymorphic restriction site, allele frequencies were similar in the hypertensive and the normotensive groups. In the absence of parental genotypes, the haplotype frequencies combining the three restriction fragment length polymorphisms were estimated by using maximum likelihood techniques and were similar in both groups (hypertensive group, 0.429, 0.277, and 0.177; normotensive group, 0.453, 0.245, and 0.195 for the three most common haplotypes). A rare haplotype detected by Taq I/Hind III was apparently more frequent in the hypertensive than in the normotensive group (hypertensive group, tH 0.086, th 0.022; normotensive group, tH 0.038, th 0.050), but the difference was not statistically significant. In conclusion, no association between renin gene polymorphisms and essential hypertension was demonstrated in the present study.
Adult↗
Arginine vasopressin gene regulation in the homozygous Brattleboro rat.
The Brattleboro rat, which has an autosomally recessive form of diabetes insipidus, has been reported to have a marked defect in the regulation of arginine vasopressin (AVP) gene expression. However, it is not known whether this is a primary genetic defect or occurs secondary to the urinary water losses which occur in the absence of circulating AVP in the Brattleboro rat. This present study was therefore undertaken to study AVP gene regulation in the Brattleboro rat after chronic AVP treatment by osmotic minipump for 2 wk. In Brattleboro rats without AVP treatment, neither urinary osmolality (Uosm) nor hypothalamic AVP mRNA was significantly changed after 24 h of fluid deprivation (Uosm, 413 +/- 33 to 588 +/- 44, NS; AVP mRNA, 39.33 +/- 2.95 to 46.39 +/- 2.71 pg/micrograms total RNA, NS). In contrast, when Brattleboro rats were treated with AVP for 2 wk, the regulation of AVP gene occurred in response to 24 h of fluid deprivation. In these studies, hypothalamic AVP mRNA was significantly increased compared with the Brattleboro rats still receiving AVP with free access of water (28.9 +/- 3.5 vs. 65.0 +/- 3.3 pg/micrograms total RNA, P less than 0.001). Further studies in Long-Evans rats demonstrate a similar response to a comparable degree of fluid deprivation as Uosm and AVP mRNA were significantly increased after 72 h of fluid deprivation (Uosm, 1,505 +/- 186 to 5,460 +/- 560 mosmol/kg, P less than 0.001; AVP mRNA, 31.7 +/- 3.9 to 77.5 +/- 4.6 pg/micrograms total RNA, P less than 0.001). These results indicate that AVP-replaced homozygous Brattleboro rats can regulate AVP gene expression normally in response to fluid deprivation. This finding indicates that the defect in AVP gene regulation in the Brattleboro rat not receiving AVP replacement is a secondary phenomenon rather than a primary genetic defect.
Animals↗
An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.
A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval.
Adult↗
Effect of the circulating renin-angiotensin system on prolactin release in humans.
We recently reported that renin, angiotensinogen, and angiotensin-converting enzyme were present in normal human pituitary lactotroph cells and PRL-secreting adenomas. Angiotensin-II and -III have also been shown to modulate PRL release in vitro. The present study was designed to determine whether angiotensin modulates PRL secretion in vivo. In 36 hypertensive patients with widely varying renin levels, active renin and basal PRL levels did not correlate. In 10 normal volunteers, both a sustained infusion of angiotensin-II and a graded infusion of angiotensin-III induced a 2- to 3-fold increase in aldosterone levels, but had no effect on PRL secretion. Administration of the angiotensin-converting enzyme inhibitor captopril had no effect on PRL circadian rhythm in 10 normal subjects or on PRL concentrations in 11 patients with PRL-secreting adenomas. Cross-over administration of placebo and captopril did not affect the peak PRL level measured after TRH treatment in 10 hypertensive men (placebo, 43.1 +/- 5.4; captopril, 40.0 +/- 6.2 micrograms/L; P = NS) or the rise in PRL induced by doperidone in 6 normal women (placebo, 129.5 +/- 16.2; captopril, 150.0 +/- 35.7 micrograms/L; P = NS). Further, administration of enalapril for 30 days to 6 hypertensive patients did not alter basal PRL concentrations or the peak concentrations induced by TRH. These data indicate that in humans the circulating renin-angiotensin system does not interact with diurnal PRL release or with the response to TRH or domperidone.
Adenoma↗