Publications by authors named "Michelakis A"

Carbadox is known to induce toxic effects on the adrenal cortex, resulting in hypoaldosteronism. To study the involvement of carbadox on the renin-angiotensin system, weaned piglets of five weeks old received feed supplemented with 0 (control group), 50, 100, 150 or 200 ppm carbadox. After four weeks the 100 and 150 ppm groups had significantly higher plasma renin activity levels than the control group and after nine weeks plasma renin activity levels of all treated groups were significantly higher than the control group.

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Normal healthy volunteers were studied after they ingested various beta-carotene doses. Daily administration of 15 or 45 mg beta-carotene resulted in significant increase in plasma beta-carotene levels. The extent of increase and the pattern of plasma beta-carotene levels showed substantial interindividual variation.

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It is generally recognized that smoking is associated with an increased risk for the development of coronary artery disease. Since it has been suggested that increased plasma renin activity (PRA) may be a risk factor for cardiovascular disease, PRA was measured in a group of smokers and nonsmokers. PRA was measured under basal conditions, following intravenous (IV) furosemide administration and after a short burst of smoking.

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Effect of smoking on the plasma levels of cortisol, growth hormone, and prolactin was evaluated in a group of smokers and nonsmokers. Plasma levels of these hormones were measured under basal conditions and following a short burst of smoking. In addition, to determine the mechanism of action of nicotine on the release of these hormones, rat renal cortical slices were incubated with nicotine and the generation of cyclic AMP was measured in vitro.

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The ultrastructural localization of renin in the juxtaglomerular apparatus of the kidney of the toad Bufo bufo has been examined using an immunogold staining method for electron microscopic immunocytochemistry and an antiserum to renin isolated from the submandibular gland of the mouse. Renin immunoreactivity was confined to lamellated granules in the cytoplasm of epitheloid or juxtaglomerular cells in the glomerular afferent arterioles and also in the media cells of larger arteries. Mouse kidney tissue, examined for purposes of comparison, showed immunolabeling limited to the granules of the juxtaglomerular cells.

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A defect in the renin-angiotensin system has been shown in diabetic patients and experimental animals, in particular with nephropathy or autonomic neuropathy. The mechanism for this low plasma renin activity (PRA) is poorly understood. In order to clarify this defect, the renin-angiotensin system was studied in alloxan-induced diabetic and age-match control mice.

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The cellular localization of renin was examined in the kidneys of some amphibians of the genus Bufo by immunoperoxidase and immunofluorescence techniques with an antiserum to renin isolated from the submandibular gland of the mouse. Immunoreactivity could be demonstrated in the media cells of the afferent arterioles (juxtaglomerular cells) close to as well as at great distance from the glomeruli. Occasionally, media cells of larger arterial vessels were also stained.

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Intravenous injection of 125I-radiolabeled submaxillary gland renin into mice resulted in rapid disappearance of this protein with a corresponding increase in its metabolites in the serum. The disappearance rate was substantially reduced after nephrectomy. Result from the in vitro incubation of the labeled renin with the whole blood excluded the possibility of any blood components participating in renin degradation.

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Effects of oral contraceptive agents (mestranol and norethindrone) on carbohydrate metabolism were evaluated in a group of 18 healthy young women. Plasma glucose, insulin, and glucagon responses were evaluated after a glucose load (oral and intravenous) and an amino acid challenge (oral and intravenous). The oral glucose tolerance was normal and was unaltered by the use of oral contraceptive agents.

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The effects of subcutaneous injection of compound 48/80 and histamine on the water intake, plasma renin activity (PRA) and plasma histamine levels were investigated in the rat. The results suggest that compound 48/80 and histamine stimulate water intake by different mechanisms. The compound 48/80-induced water intake seems to be mainly mediated by stimulation of the renin-angiotensin system.

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The present studies were undertaken to investigate the effect of prostaglandins (PGs) on renin release from the submaxillary glands of mice. Pooled mouse submaxillary gland slices were incubated in Krebs-Henseleit buffer solution following a preincubation period, and renin release was measured by a radioimmunoassay for the direct measurement of submaxillary gland renin. Arachidonic acid (AA) significantly stimulated renin release at 10, 20, and 30 min of incubation.

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Esterase release was investigated in male and female submandibular glands of 5 strains of mice (ICR/BR, ND/4BR, SW/BR, DDS/Cox and C57BL/6BR) using dispersed cells prepared by treatment with collagenase and hyaluronidase. The muscarinic-cholinergic agonist methacholine stimulated esterase release in C57BL/6BR, DDS/Cox and SW/BR females and DDS/Cox males in a dose-dependent manner, but did not stimulate esterase release in ICR/BR and ND/4BR strains of both sexes. The percentage release of esterase over control in response to methacholine in females was of the descending order: C57BL/6BR, DDS/Cox, SW/BR, ND/4BR, ICR/BR.

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Five forms of renin, A0, A, C, D and E, from mouse submaxillary gland were purified by a two-step procedure including chromatography on the immunoaffinity column and CM-cellulose column. Four renin fractions, A0, A, C and E were purified to homogeneity by the criteria of polyacrylamide gel electrophoresis, analytical isoelectric focusing and Ouchterlony double immunodiffusion. All these forms of renin have molecular weights of 40 000 as determined by gel filtration on Sephadex G-100 column.

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Tritium labeled leucine was used to investigate the effect of sodium intake on renin biosynthesis. This labeled amino acid was incubated with renal cortical slices from mice which were fed on low, basal and high sodium diets and its incorporation into the renin molecule was investigated. Renin was extracted from the incubated slices and then precipitated with rabbit anti-mouse submaxillary renin serum followed by the addition of goat anti-rabbit IgG serum.

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In this study we have shown that sodium deprivation of rats increased the number of specific granules and renin activity in atria. Sodium loading and DOCA treatment were found to lower the number of granules and renin activity. Renin activity which is present in both atria and ventricles is not localized in specific granules, as shown by ultracentrifugation and immunocytochemistry.

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PRA and the inactive renin which is activated by cold (IR-C) were studied in a group of normal subjects and in patients with diabetes mellitus with and without the presence of nephropathy. The amount of renin activity, as measured after incubation of plasma at -5 C for 4 days, was called cold renin activity (CR. PRA was measured by a standard method.

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The present studies were undertaken to explore further the role of prostaglandins in the release of renin from the renal cortex. To provide the best assessment of renin release, renin was determined by a radioimmunoassay for the direct measurement of renin. Slices of mouse renal cortex were incubated at 37 degrees C with arachidonic acid (AA), 5,8,11,14-eicosatetraenoic acid (ETA), indomethacin, prostaglandins, and synthetic prostaglandin endoperoxide analogue (EPA).

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By using antibodies against highly purified submandibular gland renin, renin was localized immunocytochemically at the light and electron microscopic level in the submandibular glands and kidneys of adult male SWR/J and C57BL/6J mice. In accord with the data of Wilson et al. (Proc Natl Acad Sci USA 75:1185, 1977), renin was demonstrable only in the submandibular glands of SWR/J mice (high strain), where it was confined to the secretory granules of the granular convoluted tubules.

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Dimethylbenz[a]anthracene was injected into the submandibular glands of male Swiss-Webster mice. From tumors obtained, three cell lines were established. Immunocytochemical stainings revealed epidermal growth factor, renin, and peptidase in a significant portion of cultured tumor cells.

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The effect of alpha- and beta-adrenergic agonists on renal and submaxillary renin of different molecular weights was studied using male albino mice as experimental animals. Phenylephrine or isoproterenol was administered intravenously after removal of the submaxillary glands and/or kidneys. Renin was isolated from plasma by column chromatography and then measured by a direct radioimmunoassay.

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