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Biomedical subjects

P Corvol

Publications and source records attributed to P Corvol.

At least 307 records · Page 17Linked to original sources
PubMed1988

Effect of thyroidectomy on rat T-kininogen.

The thyroid state affects the inflammatory reaction; in general, thyroid hormones increase and hypothyroidism decreases the inflammatory response. T-kininogen is an acute phase protein that inhibits cysteine proteases. The influence of thyroidectomy and 3,5,3'-triiodothyronine (T3)-treatment of thyroidectomized animals was examined on rat plasma T-kininogen concentration. Thyroidectomy increased the T-kininogen level three- to fourfold. A single administration of 10 micrograms T3/100 g body wt in 7-wk postthyroidectomy rats decreased it by approximately 50%. Daily treatment with 0.5 micrograms T3/100 g body wt prevented the increases in T-kininogen. The modifications in plasma T-kininogen concentration were confirmed by high-performance liquid chromatography analysis of the plasma kinins released by trypsin. They demonstrated that T-kinin was greatly and bradykinin slightly increased after thyroidectomy and that T-kinin concentration in T3-treated thyroidectomized animals was almost restored to the control level. The ability of thyroidectomized animals to produce a higher plasma T-kininogen compared with euthyroid animals was further documented when T-kininogen production was stimulated by laparotomy. This procedure resulted in a fourfold increase in T-kininogen in thyroidectomized animals compared with controls. The increase of plasma T-kininogen level after thyroidectomy results from a more active synthesis of the protein, since liver slices from thyroidectomized rats synthesized T-kininogen at a rate about two times higher than normal rats. These data may account at least in part for the diminution of the inflammatory response observed after thyroidectomy.

Animals↗
PubMed1988

Crossover design to test antihypertensive drugs with self-recorded blood pressure.

In a double-blind, within-patient study, blood pressure was measured at regular intervals at the clinic by the physician and each day at home by the patient. Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone (25 mg) and triamterene (50 mg) and the beta-blocker oxprenolol (160 mg) and the greater efficacy of the combination of the two therapies. During placebo, as well as during active treatment, blood pressure values were higher at the clinic than at home, except when the patients were taking the beta-blocker, which minimized the arousal response during blood pressure measurements in the clinic. With 2-week treatment periods, separated by 2 weeks of placebo administration, blood pressure returned toward its initial level after each of the three treatments and none of the carryover effects was significant at the 5% level. This methodology was intended to make it possible to demonstrate in 27 patients at the clinic and in 20 patients with measurements made at home, at the usual statistical risks (alpha = 5%, beta = 10%), a fall of 5 mm Hg in diastolic blood pressure in comparison with a placebo. Moreover, at the end of this 3-month follow-up, each patient could continue to receive the treatment that was the most effective and the best tolerated. In conclusion, the use of a within-patient trial design, with a 15-day washout period between active treatments and careful recording of blood pressure values, can minimize the number of patients included in hypertension trials and offer to each patient the possibility of individualization of treatment.

Antihypertensive Agents↗
PubMed1988

Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction.

To explain how converting enzyme inhibition could improve the prognosis in cardiac insufficiency, the effect of converting enzyme inhibition (CEI) by S9490-3 (Perindopril) treatment for 2 months (treated infarctions, n = 18) on hormonal plasma variables and the quantitative and qualitative changes in myocardium were studied in an experimental model of left ventricular infarction in rats (untreated infarctions, n = 18) and compared to a sham-operated control group (n = 15). Induction of myocardial infarction was associated with a transient decrease in blood pressure. CEI treatment maintained a lower blood pressure throughout the experimental period. Plasma renin concentration was not significantly increased in the untreated infarct group (155.4 +/- 136.7 ng AI/ml/hr) as compared to the sham-operated group (47.6 +/- 15.9 ng AI/ml/hr). Plasma aldosterone did not change in the three experimental groups. The plasma level of immunoreactive atrial natriuretic factor increased in the untreated infarct group (185 +/- 245 pg/ml) as compared with the control group (76 +/- 40 pg/ml) and was normalized by CEI (66 +/- 60 pg/ml). Body weight was slightly decreased in both treated and untreated infarct groups, whereas the heart weight was significantly increased in the untreated group (1,540 +/- 310 mg) and normalized by treatment (1,145 +/- 180 mg) as compared with sham-operated controls (1,071 +/- 80 mg). The combined atria and right ventricular mass was significantly increased in the untreated infarct group (660 +/- 210 mg) and decreased by treatment (443 +/- 106 mg) but was not completely normalized (controls, 343 +/- 40 mg). Left ventricular isomyosin profiles were modified by myocardial infarction as compared with controls: V1 form decreased from 62.4 +/- 9.4% in the sham-operated group to 41.6 +/- 13.4% in the infarct group, and the V3 form increased from 13.0 +/- 4.7% in sham-operated animals to 27.4 +/- 11.8% in untreated infarct animals. CEI treatment partially, but significantly, reversed this modification of the isomyosin profile (V1, 53.0 +/- 14.4%; V3, 17.5 +/- 8.0%). Volume density of collagen was significantly increased in the untreated infarct rats (4.14 +/- 0.81% versus 2.68 +/- 0.49% in controls), and this was reversed by treatment (2.95 +/- 0.66%). Messenger RNA encoding for atrial natriuretic factor, measured by dot blot hybridization, was significantly increased in both the atria and the ventricles in the untreated infarct group, and treatment by CEI partially reversed this increase. Thus, myocardial infarction profoundly modified several variables of peripheral circulation and quantitative and qualitative myocardial protein expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Differential effects of nephrectomy and surgery on plasma kininogens and angiotensinogen in the rat.

The effects of bilateral nephrectomy or a sham operation on plasma angiotensinogen and on the different kininogens were studied in the rat. Total plasma kininogen was measured by RIA of kinins after trypsin hydrolysis. In addition, the high molecular weight (HMW) kininogen and the low molecular weight (T)-kininogen were specifically quantified by using direct RIAs. Angiotensinogen was measured by RIA of angiotensin I after exhaustion by renin. Three groups of control, nonoperated, bilaterally nephrectomized and sham-operated rats were studied in each experiment. Twenty-four hours after either a bilateral nephrectomy or a sham operation total plasma kininogen was elevated approximately 5 times when compared to control rats. Time course measurements from 0 to 48 h in 3 other groups of control, bilaterally nephrectomized and sham-operated rats demonstrated that kininogen gradually increased at 12, 24, and 48 h after the surgery and that the elevation observed in plasma kininogen appeared to be entirely due to an increase in T-kininogen levels. There was no difference in T-kininogen levels between bilaterally nephrectomized and sham-operated animals. By contrast HMW kininogen was neither influenced by surgery nor by nephrectomy. Angiotensinogen increased more than 8 times in bilaterally nephrectomized rats but displayed only little changes in sham-operated animals. During the course of this experiment it was observed that also in control animals submitted to repeated skin incision and venipuncture for blood sampling at the jugular vein, T-kininogen increased dramatically in plasma, but reached values lower than in sham-operated or bilaterally nephrectomized rats. In a third experiment performed in normal rats it was found that T-kininogen levels were more than 3 times elevated over initial values 24 h after a single blood sampling at the jugular vein. These results indicate that T-kininogen but not HMW kininogen is very sensitive to surgery, perhaps as a result of increased T-kininogen synthesis due to an inflammatory reaction. The T-kininogen might participate in the inflammatory reaction that occurs at the site of tissue injury and in the healing process. As there was no difference in T-kininogen, and in HMW kininogen levels between bilaterally nephrectomized and sham-operated rats, the kidneys do not seem to play an important role in the regulation of plasma kininogens. Angiotensinogen, HMW kininogen, and T-kininogen are therefore regulated separately after nephrectomy or surgery.

Angiotensinogen↗
PubMed1988

Isolation and characterization of renin-producing human chorionic cells in culture.

Chorionic tissue is one of the major extrarenal sites of renin production, and as such, cultured chorionic cells are a potential model for in vitro studies of renin biosynthesis and regulation. Human chorionic cells were isolated from four chorions and maintained in tissue culture for a total of eight subcultures. Total renin production was considerable in the primary cultures, but fell gradually with successive passages. The cells could be frozen and thawed without losing their ability to divide or produce renin. Both the primary cultures and the subcultures contained a single type of elongated cell containing abundant rough endoplasmic reticulum and myofibrils, but no renin granules, suggesting that the cells had smooth muscle-like features. Immunocytochemistry indicated that they contained both renin and prorenin. The renin produced by the chorionic cells was not stored within the cells, but was released rapidly into the medium. More than 95% of the renin produced was prorenin, which, after activation, had biochemical and immunological properties similar to those of pure human renin. The cells contained a renin mRNA that had the same size as that for renal renin (1.6 kilobases), confirming the synthesis of renin by these cells. The cells were also examined for the presence of other components of the renin-angiotensin system. Angiotensinogen and angiotensin I were not detected, but angiotensin-converting enzyme was present in extracts of primary and secondary cultured cells. beta hCG and progesterone were also found in the medium of primary culture. However, the production of beta hCG and progesterone fell after the primary culture, and beta hCG and progesterone were indetectable in secondary and tertiary cultures, respectively. These experiments suggest that these two hormones do not influence renin synthesis or vice versa. Thus, these cultures of human chorionic cells synthesized considerable quantities of prorenin and can provide a permanent source of nonrenal prorenin-producing cells.

Cell Separation↗
PubMed1988

Molecular biology as a tool for genetic research in hypertension: application to the renin gene.

Hypertension is a multifactorial and heterogeneous disease caused by the addition of environmental and genetic factors. Heritability of systolic and diastolic blood pressure has been well established. Among 6,594 hypertensive patients studied in our clinic, 42% had a history of hypertension in one of their parents and in this group, 13% also had a hypertensive sibling. Anamnestic but not clinical features of patients with familial hypertension slightly differ from patients without familial hypertension. A general strategy is proposed to test the hypothesis that genes known to regulate blood pressure are also responsible for liability to hypertension. In a preliminary report, a study of the TaqI polymorphism of the human renin gene did not reveal a significant difference between hypertensive patients with a family history of hypertension and normotensive controls. A linkage study with DNA markers in informative families is also proposed as an alternative.

Humans↗
PubMed1988

[Kallikrein-kinin system, the kidney and arterial pressure].

Renal kallikrein is synthetized in the distal nephron and secreted in urine. Studies on the microdissected nephron and on the whole kidney using immunohistochemistry indicate that kallikrein is produced at the level of the distal part of the distal tubule and in some species in the cells of the initial part of the collecting duct. Urinary kinins are formed at these same sites. The renal tubule contains high levels of kininases, able to inactivate kinins, but the kininases are located mainly up-stream the sites of kinin production, i.e. in the glomerulus and in the proximal tubule. A kininase activity is however also found in the medullary collecting duct. This collecting duct kininase activity might contribute to the control of kinin levels in kidney and urine. The physiological role of the renal kallikrein kinin system is not completely understood. There is some evidence for a role of urinary kinins in water and solute transferrence in the distal nephron. Also kinin production in the renal interstitium and/or circulation may contribute to the control of renal blood flow. In the isolated perfused rat kidney vasoconstricted by angiotensin II for example, the high molecular weight kininogen is hydrolyzed to release kinins and induces a vasodilatation. The kallikrein-kinin system therefore might play a role in kidney function by antagonizing the vascular effect of angiotensin II in the renal circulation and the maintenance renal blood flow.

Animals↗
PubMed1988

[Immunologic approach of the blockage of the renin angiotensin system in vivo].

To block the renin-angiotensin system by antibodies directed against renin or angiotensins is an old and recent goal. This goal can be attained by passive transfer of antibodies or by active immunization against the different molecules of the system. Only passive transfer of polyclonal antibodies directed against the native substrate (angiotensinogen) has been performed in rats. This acute blockade of angiotensinogen substrate availability decrease blood pressure about 30 mmHg in salt depleted rats. Passive transfer of anti-converting enzyme immunoglobulins has been already performed in rabbit and rat. It induced an immunoallergic reaction in the pulmonary capillary bed. Immunization against angiotensin II has been a powerful tool in the exploration of the role of the renin angiotensin system in hypertension. Passive and active immunization have been performed in different species: rabbit, rat. The majority of the results concerning the decrease in blood pressure was negative. However, some works reported positive results which could be related to the high affinity of antibodies for angiotensins. Passive and active immunizations against renin were also performed in different species: dog, pig, rat, rabbit, primates. The majority of the results concerning the decrease of blood pressure were positive, if species specificity of renin was taken into account. Recently passive transfer of polyclonal and monoclonal antibodies, directed against human renin have been performed in normotensive and hypertensive primates, demonstrating an acute fall in blood pressure comparable to that observed with converting enzyme inhibitors. Active immunization against human renin has also been performed in primates; and the chronic blockade of the renin-substrate reaction obtained in this way was associated with a significant decrease in blood pressure, aldosterone secretion and a disappearance of plasma renin activity. Unfortunately, such an active immunization was associated with an organ specific autoimmune disease within the kidney. In conclusion, passive and active immunization against the different proteins and peptides of the system offers specific models of blockade which can be compared with synthetic inhibitors of renin, converting enzyme and angiotensins. Therapeutic application of this immunological approach necessitates the verification of the total absence of autoimmune disease.

Angiotensinogen↗
PubMed1988

[Transluminal angioplasty in renovascular hypertension with renal insufficiency].

From 1985 to 1986, 71 patients with renovascular hypertension were treated by percutaneous transluminal angioplasty (PTA). Among them, 13 (mean age 67 +/- 7 years) had a hypertension refractory to drug therapy (blood pressure: 194 +/- 33/103 +/- 15 mmHg) associated with an impaired renal function (creatinine clearance: 33 +/- 20 ml/mn). Ten had a stenosis in a solitary functioning kidney and a contralateral renal artery thrombosis. Three had bilateral renovascular stenosis. All patients had severe diffuse atherosclerotic disease, i.e. coronary heart disease (n = 7), carotid artery stenosis (n = 6), abdominal aortic aneurysm (n = 3) or arteritis (n = 5). Among these 13 patients, PTA could not be performed in one patient (failure to catheterize the stenosis) and two immediate renal artery dissections were observed: the first was accompanied by a thrombosis of the renal artery which could be successfully treated in emergency by surgical revascularization. The second occurred in a segmental renal branch and did not require surgery since it did not induced further impairment of renal function. Among the 10 remaining patients, nine PAT were classified as immediate angiographic success. One incomplete result required a second PTA 6 months later. Three important inguinal hematomas were observed and blood transfusion was required in 2. Seven patients have been reevaluated after a follow-up of 3 to 22 months. Restenosis occurred in two patients, 6 and 20 months respectively after PTA. A successful surgical revascularization was performed in these 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Epithelioid sarcoma of soft tissues: a case of extrarenal renin-secreting tumour.

The case of a young woman presenting with a renin-secreting soft tissue sarcoma is described. The primary extrarenal tumour as well as metastatic disease were associated with severe hypertension and both required surgical treatment. The location of these rare malignant tumours and their association with renin-dependent hypertension is discussed. In cases of this type, reappearance of hypertension suggests tumour recurrence.

Adolescent↗
PubMed1988

[Acute response to calcium inhibitors in secondary arterial hypertension: does renin play a role?].

Calcium channel blocking agents are considered to be particularly effective in reducing blood pressure (BP) in low renin essential hypertension and in primary aldosteronism. The aim of this study was to compare the acute BP response to nicardipine in 2 opposite situations of stimulation of the renin angiotensin system: eight patients (49 +/- 13 years, mean arterial BP (MAP) 123 +/- 8 mmHg) with primary aldosteronism (active renin less than 5 pg/ml, group 1) and nine patients (38 +/- 17 years, MAP: 107 +/- 13 mmHg) with renovascular hypertension and high level of active renin (greater than 25 pg/ml, group 2). They had not taken any antihypertensive treatment since at least one week. After 60 minutes in the supine position (T0) nicardipine was infused at a rate of 7.5 mg/h during 10 minutes (T10), 15 mg/h from the 10th to 20th minute (T20) and 30 mg/h during the last ten minutes (T30). Thus, a total cumulative dose of 8.75 mg was administrated in 30 minutes. BP was recorded by an indirect oscillometric method (Sentrom) every 2 minutes and renin was assayed through an immuno-radiometric procedure (IRMA). There was an important and similar BP fall in the 2 groups (Gr 1: T10-6 p. 100, T20-17 p. 100, T30-25 p. 100; Gr 2: T10-7 p. 100, T20-13 p. 100, T30-18 p. 100) with a very significant dose-effect relation (r = 0.67, p less than 0.001). There was also an important increase in heart rate similar in the 2 groups (+35 p. 100, +25 p. 100, ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Comparison of 3 methods of blood pressure measurement in obesity].

Arm girth and circumference often leads to difficulties in Blood Pressure (BP) measurement in obese patients. In order to assess the best method of BP measurement, we have compared in a triplicate study, Intra-arterial Pressure (INTRA) to indirect measurements: Mercury Sphygmomanometer (SPH) and oscillometric device Bard Sentron (SEN). SPH and SEN were successively connected to the same cuff (inflatable bladder 14 x 31 cm). Cuff was positioned on contralateral arm to arterial puncture. 19 subjects were studied (18 female); mean age was 51.3 +/- 9 years (extremes: 37-69), mean weight 104 +/- 19 kg (84-147), weight index 40 +/- 4.7 kg/m2 (34-49), and brachial circumference 39 +/- 4 cm (33-47). First out-patient mean blood pressure measurement was 182/104 mmHg (148-264/80-132). Mean SPH BP were 158 +/- 34/91 +/- 3 (98-230, 72-112) and mean INTRA: 171 +/- 37/85 +/- 5 (122-256/56-118). Mean systolic and diastolic differences (S, D, mmHg) were: (Table: see text). 1) SPH systolic BP underestimates HUM systolic BP. 2) Mean SEN measurements are very closed to HUM values. 3) A great intra-individual variability occurs since more than 50 per cent systolic SPH values show discrepancy of more than 10 mmHg for systolic and diastolic HUM BP; the same discrepancies occur for SEN vs HUM. 4) Differences between couples of values (HUM-SEN, HUM-SPH) are not correlated to BP level, neither for systolic nor for diastolic BP. 5) No significant correlation occurs when BP deltas are compared to weight index or arm circumference.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Malignant adrenal cortex carcinoma revealed by an isolated picture of primary hyperaldosteronism].

Adrenocortical carcinoma (ACC) is a rare disorder with an estimated incidence of only 0.023 percent of all malignancies. In most cases, Cushing's syndrome and virilization or feminization due to abnormal steroid production by the tumor rapidly lead to the diagnosis. Occasionally, the tumor produces an excessive amount of mineralocorticoids only and ACC can be revealed by an isolated syndrome of primary aldosteronism. Out of 100 cases of tumoral primary aldosteronism studied from 1977 to 1987, we observed 4 ACC and 96 Conn's adenomas (CONN). When primary aldosteronism was diagnosed, ACC and CONN had same clinical features, although hypokalemia in ACC was more profound: 2.2 +/- 0.76 mmol/l (1.4 to 3.2) compared to 2.9 +/- 0.5 (1.6 to 4.2) in CONN. Mean supine plasma aldosterone levels, plasma renin and aldosterone responses to the upright posture or to serum saline infusion, cortisol at 8 a.m. were not different in patients with ACC from those observed in patients with CONN. 24 hours urinary cortisol excretion and 17-ketosteroids excretion were highly increased in three out four patients with ACC. Clinical, biological and hormonal investigations were therefore not sufficient to diagnose malignant tumoral primary aldosteronism. Systematic computed tomographic scanning allowed to differentiate carcinomas from adenomas on the following criteria: ACC showed enlarged tumor size that was always above 30 mm in diameter, whereas the largest CONN measured 20 mm.ACC appeared as an heterogeneous tumor with the presence of internal calcifications in each case of ACC, that were diagnosed both on ultrasound and CT scan, whereas none of the CONN showed any calcification, using the same screening procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Ketosteroids↗