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Biomedical subjects

J Menard

Publications and source records attributed to J Menard.

At least 163 records · Page 9Linked to original sources
PubMed1982

Diuretic and natriuretic effects of nifedipine on isolated perfused rat kidneys.

The effects of nifedipine, a vasodilating drug which acts through calcium antagonism, were studied in vitro using isolated perfused rat kidneys. Most of the nifedipine was neither metabolized nor excreted by this preparation. Four doses were tested: 50, 250, 500 and 750 nM. The two higher concentrations enhanced urine flow and sodium (UNaV) and potassium excretion. Tubular reabsorption of sodium was reduced compared to untreated control kidneys. The glomerular filtration rate was not modified but the filtration fraction decreased. The magnitude of urine volume, UNaV, urinary potassium excretion and filtration fraction changes were related to the dose of nifedipine. The decrement of total renal resistance and the increment of UNaV were correlated for 500 and 750 nM nifedipine (n = 13; r = -0.77; P less than .001), suggesting that it acted by dilating the renal vascular bed. Nifedipine at 250, 500 and 750 nM significantly increased the renin secretion rate compared to that of untreated control kidneys. When renin secretion was enhanced by 50 nM isoproterenol, this stimulatory effect was enhanced in kidneys concomitantly treated with 500 and 750 nM nifedipine. Dihydralazine, another vasodilating drug, was tested at a comparable molar dose (500 nM) and induced similar changes in urine volume, UNaV, urinary potassium excretion and Na reabsorption. The variations in total renal resistance and UNaV were also inversely correlated (n = 8; r = -0.68; P less than .05). Dihydralazine did not modify renin secretion rate significantly. These results suggest that: 1) both nifedipine and dihydralazine increase diuresis, natriuresis and kaliuresis in the isolated perfused rat kidney and 2) nifedipine enhances basal renin release from the juxta-glomerular cells and potentiates renin release caused by beta receptor stimulation.

Animals↗
PubMed1981

Rat angiotensinogen and des(angiotensin I)angiotensinogen: purification, characterization, and partial sequencing.

Rat angiotensinogen was completely purified by a six-step procedure including (1) ammonium sulfate precipitation, (2) affinity chromatography on Affi-gel blue, (3) chromatography on DEAE-Sephacel, (4) chromatography on hydroxylapatite, (5) chromatography on Ultrogel AcA 54, and (6) isoelectric focusing. Two peaks of pure angiotensinogen were obtained, distinguishable by their isoelectric points (4.55 and 4.75). Both contained 23 microgram of angiotensin I/mg of protein. Sodium dodecyl sulfate--polyacrylamide gel electrophoresis of the peak with pI = 4.55 revealed two protein bands (respectively Mr 57000 and 59000) and a single protein band (Mr 57000) for the peak with pI = 4.75. The molecular weight of the latter homogeneous form, as determined by sedimentation equilibrium, was 55000. Only one immunoprecipitin line was observed when antiserum reacted with the heterogeneous angiotensinogen in Ouchterlony gels. The first 17 amino acids of the N-terminal region of the angiotensinogen with pI = 4.75 are reported. The amino acids in positions 10 and 11 which correspond to the renin cleavage site are leucyl-leucyl. The des(angiotensin I)angiotensinogen obtained after hydrolysis of angiotensinogen with pure mouse submaxillary gland renin was found to consist of a single protein band with an Mr of 56000 as revealed by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Only one N-terminal residue (leucyl) was obtained for this des(angiotensin I)angiotensinogen. These findings establish that renin only cleaves angiotensinogen at a single site.

Amino Acid Sequence↗
PubMed1981

Measurement of urinary kallikrein activity. Species differences in kinin production.

A sensitive, specific radioimmunoassay for kinins has been developed, which is able to detect 1.5 pg bradykinin or 3 pg lysyl-bradykinin (Lys-bradykinin). 50% displacement in the standard curve was obtained with 10 pg bradykinin or 15 pg Lys-bradykinin in 0.6-ml incubates. The antisera, raised against bradykinin, recognized well Lys-bradykinin and methionyl-lysyl-bradykinin (Met-lys-Bradykinin), but cross-reacted 0.4% or less with bradykinin fragments. Kininogen cross-reacted only 0.2%. The radioimmunoassay and kininogen from several species were used in the measurement of human and rat urinary kallikrein activity. The peptide generated by hydrolysis of the substrates by rat or human urines was characterized by radioimmunoassay in two different systems: polyacrylamide gel electrophoresis and carboxymethyl cellulose chromatography. Both urines did not produce the same kinin: the kinin produced by human urine migrated like Lys-bradykinin, whereas the kinin produced by rat urine migrated like bradykinin. This gives evidence of differences in the specificity between kinin-forming enzymes in rat and human urines.

Animals↗
PubMed1981

New renin inhibitors homologous with pepstatin.

Four homologues of pepstatin, the potent but poorly soluble inhibitor of aspartic proteinases, were synthesized by coupling to the C-terminus of the natural pentapeptide the following amino acid residues: L-arginine methyl ester, L-aspartic acid, L-glutamic acid and the dipeptide L-aspartyl-L-arginine. The peptide-coupling reagent we used, benzotriazolyloxytris(dimethylamino)phosphonium hexafluorophosphate, allowed us to obtain readily pure pepstatin homologues with high yields (60-83%). Pepstatylarginine methyl ester and pepstatylglutamic acid were about one order of magnitude more water-soluble than pepstatin. The four homologues and pepstatin were tested in vitro as inhibitors for highly purified pig and human renins acting on the N-acetyltetradecapeptide substrate. The 50% inhibitory concentrations (IC50) of the homologues were ranged from 0.01 to 1 microM against porcine renin at pH 6.0 (pepstatin IC50 approximately 0.32 microM) and from 5.8 to 41 microM against human renin at pH 6.5 (pepstatin IC 50 approximately 17 microM). By three different graphical methods we showed that pepstatin and the four homologues behaved as competitive inhibitors for porcine renin. The most potent inhibitors were pepstatylaspartic acid and pepstatylglutamic acid, with inhibitory constants respectively 2- and 10-fold smaller than that of pepstatin. By coupling glutamic acid to pepstatin, the ratio solubility/Ki was increased by two orders of magnitude.

Animals↗
PubMed1981

[Measurement of antidiuretic hormone and plasma renin activity in desert rodents].

Plasma antidiuretic hormone (ADH) and renin activity (PRA) were determined in two species of desert rodent (Jaculus orientalis and Jaculus deserti) under chronic dehydration and were compared to those of Wistar Rat. ADH concentration was very high in the desert animals: 200 times higher than in the Rat on a normal diet and 20 times higher than in the 48 hours-dehydrated Rats. The neurohypophyseal ADH content of these rodents was twice that of the normally hydrates Rat, while the dehydration caused a decrease of neurohypophyseal content in the Rat. Plasma renin activity was respectively 2.6 and 3.7 times higher in Jaculus deserti and Jaculus orientalis than in Rats on normal diet, but it was similar to that of dehydrated Rats. During an experimental chronic dehydration, the renin angiotensin system is moderately activated in the desert rodents; but, there is an intensive stimulation of ADH which may play a primordial role in the maintenance of water balance. Now it is necessary to demonstrate how these mechanisms are involved in the natural environment of the animals.

Animals↗
PubMed1981

[The renin-angiotensin system and its inhibition (author's transl)].

The recent development of several inhibitors of the renin-angiotensin system has perfected our knowledge of the part played by this system in the control of physiological and pathological arterial pressure. Peptides inhibiting angiotensin II, such as Sar1, Ala8 angiotensin II, block the peripheral effects of angiotensin on vascular renal and adrenal receptors. Inhibition of the conversion enzyme, notably with captopril, prevents the formation of angiotensin II from angiotensin I and also results in accumulation of a vasodilator and natriuretic peptide: bradykinin. Finally, it is now possible to inhibit more specifically the reaction of renin with its substrate, angiotensinogen, by using pepstatin or its derivatives, or peptide analogues of the substrate. The use of these inhibitors, especially captopril (so far the most studied), has made it clear that renin plays a part in experimental and human essential hypertension and participates in the control of arterial blood pressure in subjects with normal sodium intake.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1981

Biochemical tests for diagnosis of phaeochromocytoma: urinary versus plasma determinations.

Fifteen patients with hypertension due to phaeochromocytoma and 35 controls with essential hypertension were studied to assess the diagnostic value of urinary and plasma biochemical determinations in phaeochromocytoma. In every case of phaeochromocytoma the urinary concentration of vanillylmandelate, metanephrines, or adrenaline plus noradrenaline was diagnostic of the disease irrespective of whether the patient was normotensive or hypertensive at the time. Plasma determinations of adrenaline and noradrenaline, however, gave falsely negative results on three occasions. These findings suggest that urinary biochemical determinations--particularly of metanephrines--are more reliable than plasma catecholamine measurements as a test for phaeochromocytoma. The test is particularly useful in patients with intermittent hypertension.

Adrenal Gland Neoplasms↗
PubMed1981

Antihypertensive and hormonal effects of single oral doses of captopril and nifedipine in essential hypertension.

In a single-dose crossover study Captopril (SQ 14225), 1 mg/kg body weight, and Nifedipine (Bay a 1040) 20 mg were administered orally to 12 hospitalized patients with essential hypertension (Stage 1 or 2, W.H.O.). Both drugs significantly reduced blood pressure, but each dose acted differently: the mean maximum arterial pressure reduction was faster and greater with Nifedipine than with Captopril: -23 +/- 2% at 37 +/- 15 min and -17 +/- 1% at 86 +/- 25 min, respectively. Captopril inhibited angiotensin II and aldosterone production, but did not accelerate heart rate or stimulate vasopressin release. Nifedipine stimulated vasopressin release and increased heart rate, but the renin angiotensin aldosterone system was not significantly affected. The blood pressure reduction was related to the initial level of activation of the renin angiotensin system only for Captopril. The blood pressure reduction induced by one drug was not related to that produced by the other in the same patient.

Administration, Oral↗
PubMed1981

Renin localization in segmental renal hypoplasia. Immunohistochemical demonstration in two cases.

The distribution of renin in two cases of segmental renal hypoplasia was investigated by immunofluorescence and the peroxidase anti-peroxidase (PAP) method using an anti-human renin antiserum. Renin-containing cells were found only in hypoplasic segments in the vicinity of altered glomeruli and small arteries. Well-preserved renal cortex and areas of chronic atrophic pyelonephritis failed to show any demonstrable site of renin production. Whatever is the mechanism of the disease, the characterization of large numbers of renin-containing cells in the affected kidney support a role for the renin-angiotensin system stimulation in this form of hypertension.

Adolescent↗
PubMed1981

Activation of renin in an anaplastic pulmonary adenocarcinoma.

1. Biochemical characteristics of a renin-like enzyme secreted by a pulmonary adenocarcinoma have been studied. A very high renin content was revealed by both enzymatic (10.4 Goldblatt units/g of tissue) and direct radioimmunoassay of immunoreactive renin (23 Goldblatt units/g of tissue). 2. The higher value by direct radioimmunoassay suggested the presence of an inactive form of the enzyme. Indeed 40--100% activation occurred with treatment by trypsin or pepsin or prolonged dialysis at pH 7.4 with or without prior acid dialysis. This neutral activation was completely abolished by a serine proteinase inhibitor. 3. A large fraction of the renin in this tumour is inactive. In comparison with other prohormones produced in tumours the findings support strongly the proposition that renin passes through a proenzyme step in synthesis.

Adenocarcinoma↗
PubMed1981

Reduction of plasma and urinary vasopressin during treatment of severe hypertension by captopril.

Plasma concentrations and urinary excretion rate of vasopressin (VP) were examined in ten cases of severe hypertension before and during short-term treatment by Captopril (SQ 14225). Before Captopril, plasma and urinary VP were high (respectively 5.24 pmol/l and 68 pmol/day) and positively correlated to plasma renin activity (PRA) and plasma aldosterone (PA). The decline in blood pressure (mean -15%) after Captopril was correlated not only to initial PRA and PA values, but also to plasma (r = 0.89; P less than 0.001) and urinary (r = 0.78; P less than 0.01) VP values. The initial dose of Captopril (1 mg/kg) induced a rapid decrease in blood pressure whereas plasma VP did not rise and aldosterone decreased. At the eighth day of Captopril treatment (mean daily dose 6 +/- 1.5 mg/kg) the drop in blood pressure (-12%) and in aldosterone persisted together with a significant reduction in plasma (1.18 pmol/l; P less than 0.01) and urinary (25 pmol/day; P less than 0.01) VP. It is suggested that these sustained simultaneous reductions in the rates of secretion of vasopressin and aldosterone are both elements of the antihypertensive effect of Captopril.

Adolescent↗
PubMed1981

The renin-angiotensin system in thyroidectomized rats.

The influence of thyroidectomy on the renin-angiotensin system was studied in the rat. From 1-6 weeks after thyroidectomy, PRA and plasma renin substrate (PRS) decreased, but the plasma renin concentration remained unchanged, and the renal renin content increased. T3 injection corrected the changes in the plasma renin-angiotensin system of thyroidectomized rats within 20-40 h. After ethinylestradiol treatment, the PRS in thyroidectomized rats rose in the same proportion as that in normal rats, but remained below the normal level. After binephrectomy, on the other hand, the PRS was high, and PRS levels in normal and thyroidectomized animals were similar. Isoproterenol increased PRA and plasma renin concentration in control animals but had no effect on thyroidectomized rats. From the above results it may be concluded that angiotensinogen production is dependent on thyroid hormones and that renin release depends on beta-adrenergic receptor sensitivity to catecholamines, which is reduced by thyroidectomy. (Endocrinology 108: 647, 1981)

Angiotensinogen↗
PubMed1981

Monoclonal antibody against human renin.

By spleen cell fusion with NS1 myeloma, a mouse hybridoma was obtained which secretes an antibody directed against human renin. This monoclonal antibody recognizes human and monkey renin, but neither hog nor mouse. Preliminary experiments demonstrate the potential of this antibody for renin immunopurification and characterization.

Animals↗
PubMed1981

Immunohistochemical characterization of renin-containing cells in the human juxtaglomerular apparatus during embryonal and fetal development.

Thirty kidneys from nine embryos, 20 fetuses, and one full-term baby were examined for their renin content by immunofluorescence and the peroxidase antiperoxidase method, using an antihuman renin antiserum. Renin-containing cells were found in the early metanephros (5-week-old fetuses). Most of them were located in the wall of well-developed renal arteries in the vicinity of the prospective vascular pole of the glomeruli. In the poorly differentiated peripheral renal cortex, intracellular fluorescence was seen in nearby arterioles of pocket-like s-shaped tubules. Rarely, labeled cells were found in the wall of major branches of renal arteries. In all locations, the renin-containing cells appear to be clearly linked to the development of the renal vascular system.

Cell Differentiation↗