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Biomedical subjects

A M Michelakis

Publications and source records attributed to A M Michelakis.

At least 19 recordsLinked to original sources
PubMed1989

Changes in plasma renin activity and renal immunohistochemically demonstrated renin in carbadox treated pigs.

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. Five and 10 weeks after carbadox administration, three and two pigs, respectively, of all groups were necropsied and the kidneys were screened for immunohistochemically demonstrated renin. All dosed pigs demonstrated an increase of immunoreactive renin, which was dose- and time-related. From these results it is concluded that carbadox induces activation of the renin-angiotensin system, secondary to the suppressing effect on mineralocorticoid secretion and that these changes may be responsible for part of the clinical picture.

Administration, Oral↗
PubMed1986

Hormonal effects of smoking--I: Effects on plasma renin activity.

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. In addition, the effect of nicotine on renin secretion was evaluated in vitro. Smoking was associated with a significant increase in pulse rate and systolic blood pressure, but no significant change in diastolic blood pressure in both groups. Basal PRA was similar among smokers and was not significantly influenced by smoking in either group. PRA increased significantly following IV administration of furosemide, but there was no significant difference between the two groups. Incubation of rat kidney slices with nicotine also did not result in increased renin secretion. These findings confirm that smoking affects the cardiovascular system, but no significant effect of smoking on PRA was observed both in vivo and in vitro experiments. These findings suggest that the increased risk for the development of coronary artery disease associated with smoking is not mediated by increased PRA.

Adult↗
PubMed1986

Hormonal effects of smoking--II: Effects on plasma cortisol, growth hormone, and prolactin.

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. Increasing concentrations of nicotine in the incubation medium resulted in increased generation of cyclic AMP. Basal levels of plasma cortisol were similar for both smokers and nonsmokers. After smoking, the cortisol levels increased significantly among smokers only and the levels achieved were significantly higher compared with nonsmokers. Mean prolactin curves were higher among nonsmokers compared with smokers, whereas growth hormone levels were similar in the two groups. These data suggest that the effects of smoking on pituitary/adrenal hormones differ among smokers and nonsmokers and that these effects may be mediated through increased generation of cyclic AMP induced by nicotine.

Adult↗
PubMed1985

Increase of plasma renin activity after subcutaneous application of compound 48/80 in the rat.

Subcutaneous (s.c.) administration of compound 48/80 (3.0 mg/kg) to conscious rats produced a time-dependent long-lasting increase of plasma renin activity (PRA). A dose-related increase of the hematocrit was also observed after injection of compound 48/80. The onset of the hematocrit increase preceded that of PRA increase. Pretreatment with a dose of more than 20 mg/kg of histamine H1-receptor antagonists such as tripelennamine or diphenhydramine prior to the injection of compound 48/80 (3.0 mg/kg s.c.) attenuated or abolished the effects of compound 48/80 on PRA, hematocrit and plasma extravasation. Pretreatment with cimetidine (histamine H2-receptor antagonist, 40 mg/kg i.p.) had no effect on these plasma variables. The increase of PRA caused by s.c. administration of compound 48/80 was not affected by the pretreatment with propranolol (beta-adrenoceptor antagonist, 10 mg/kg i.p.), which completely inhibited the isoproterenol (0.5 mg/kg s.c.)-induced PRA increase. Administration of compound 48/80 did not induce a significant PRA increase in the nephrectomized rats although the increase of hematocrit following s.c. administration of compound 48/80 persisted despite the absence of kidneys. S.c. administration of compound 48/80 (3.0 mg/kg) led to a significant decrease of histamine content at the site of injection and to a significant increase in plasma histamine concentration without affecting arterial blood pressure. The present data suggest that s.c. administration of compound 48/80 stimulates the release of histamine from cutaneous mast cells, which cause an increase in vascular permeability to plasma protein via the stimulation of histamine H1-receptors, then leads to hypovolemia. The resulting hypovolemia may directly stimulate the juxtraglomerular cells of the kidney to release renin.

Animals↗
PubMed1985

Immunohistochemical demonstration of renin in the juxtaglomerular apparatus of three Bufo species.

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. The immunohistochemical data seem to be in accordance with earlier results obtained with a modified silver impregnation technique (Movat's staining procedure) used for the visualization of juxtaglomerular cells in non-mammalian vertebrates. Mouse kidney tissue, studied for purposes of comparison, showed renin-immunoreactivity as described by earlier investigators, i.e., immunoreactive staining in the afferent arterioles near the glomeruli and in the proximal tubule cells.

Animals↗
PubMed1985

Immunoelectron microscopic localization of renin in the juxtaglomerular cells of the amphibian Bufo bufo.

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. The presence of renin or a renin-like substance in the juxtaglomerular granules of the toad kidney is discussed in relation to the lysosomal nature of these granules. A model is presented linking the lysosomal function of the juxtaglomerular granules and the release of renin mediated by beta-adrenergic receptors present on the surface of the juxtaglomerular cells.

Animals↗
PubMed1985

Multiple defects in the renin-angiotensin system in alloxan-diabetic kidney.

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. In diabetic animals, kidney renin activity (KRA) was significantly lower than that of the controls, while plasma renin substrate (PRS) concentration was slightly higher and PRA was normal. The amount of injected radiolabeled renin extracted by the kidney was normal, but the amount extracted by the liver was significantly decreased in diabetic animals. On the other hand, the degradation of the extracted renin by both the kidney and the liver was elevated as compared to the controls. This high degradation rate was accompanied by a slight increase in lysosomal protease activity in the kidneys. In in vivo studies, isoproterenol-induced PRA was 20-fold in control animals. In diabetics, isoproterenol-induced PRA was attenuated and rose only four- to fivefold over basal level. The angiotensin converting enzyme (ACE) activity in the kidney was significantly decreased in the diabetic state. It is concluded that there were multiple defects in the renin-angiotensin system in this diabetic model, namely, a depletion of renin storage with subsequent loss of maximal responsiveness to the adrenergic agonist in renin release, an elevation of intrarenal renin degradation together with a deficiency in ACE which would possibly lead to a decrease in intrarenal formation of angiotensin II.

Animals↗
PubMed1984

Role of kidney and liver in degradation of circulating submaxillary renin in mice.

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. During the in vivo study, the kidneys were found to accumulate fivefold to sevenfold more radioactivity than the liver. The degradation of the labeled renin by the kidney and the liver was studied in vitro in slice preparations after preloading of the protein into organs in vivo for 15 min. Formation of metabolites was followed by the determination of the trichloroacetic acid-soluble radioactivity. Results from these in vitro experiments suggested that both tissues had about the same capacities to degrade the accumulated renin. A substantial amount of this renin-degradation activity could be inhibited by the metabolic energy inhibitors, sodium azide and 2,4-dinitrophenol, and the lysosomal inhibitor, chloroquine. The lysosomal localization of the organ-accumulated renin after subcellular fractionation further implied the active internalization of the protein into lysosomes. Although the efficiency for renin degradation by both types of tissue were about the same, the in vivo uptake of labeled renin by the kidneys surpassed the uptake by the liver by severalfold. It is concluded that the kidneys play a major role in the degradation of circulating submaxillary gland renin.

Animals↗
PubMed1983

Effect of oral contraceptives on plasma glucose, insulin, and glucagon levels.

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. However, following intravenous administration of glucose, plasma glucose levels were slightly but significantly elevated when subjects were using oral contraceptives. Plasma insulin concentrations were slightly but significantly higher than control values in response to oral and intravenous administration of glucose while subjects were using oral contraceptives. Plasma glucagon concentrations in response to oral and intravenous glucose were similar whether the subjects were using oral contraceptive agents or not. No significant differences from control values were observed after oral and intravenous amino acid challenges when subjects were using oral contraceptive agents. Mild elevations of glucose and insulin without any significant change in glucagon concentrations suggest that glucagon levels do not play a major role in the development of insulin resistance seen in some patients using oral contraceptive agents.

Administration, Oral↗
PubMed1983

Different effects of compound 48/80 and histamine on plasma renin activity.

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. On the other hand, the histamine-induced water intake seems to be directly mediated by its action in the brain.

Animals↗
PubMed1983

Intraspecies variation in methacholine-stimulated esterase release from mouse submandibular gland.

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. There was a close relationship between the percentage release of esterase by methacholine and the esterase activity in homogenate of submandibular gland. The lower the esterase content in the homogenate of mouse submandibular gland, the higher the percentage release of esterase by methacholine stimulation in the dispersed cells.

Animals↗
PubMed1983

Prostaglandins and renin release from submaxillary glands in vitro.

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. These increases of renin release were abolished by the presence of indomethacin. The synthetic prostaglandin endoperoxide analogue (EPA) strongly stimulated renin release at 10, 20, and 30 min of incubation. However, at a higher concentration the stimulating effect of EPA virtually disappeared. PGI2 caused the highest increase of renin release at 10 and 20 min of incubation. At higher concentrations the effect of PGI2 on renin release was drastically reduced, although it was still statistically significant. PGE2 and PGF2 alpha also exerted a significant increase in renin release; however, the extent of this effect was much less than that of EPA and PGI2. Other prostaglandins such as PGE1, PGA2, PGD2, PGF1 alpha, and 6-keto-PGF1 alpha were found to have no significant effect on renin release. These results suggest that the prostaglandin system directly affects renin release from submaxillary gland independent of systemic hemodynamic and neurogenic influences.

Animals↗
PubMed1982

The purification and characterization of multiple forms of mouse submaxillary gland renin.

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. No high molecular weight renin could be demonstrated. Individual renin fractions showed similar angiotensin I formation activity, 52-158 ng angiotensin I/ng protein per h. No other protease activity could be detected with hemoglobin or casein as substrate. These purified proteins showed a discrete pattern of migration under polyacrylamide gel electrophoresis. Under denaturing condition in SDS-gel electrophoresis, all but fraction D showed a protein band with a molecular weight of 30 000. Fraction D showed a major component with molecular weight of 33 000. The isoelectric points of these renin forms varied from 5.46 to 5.76. They all reacted with antibody raised against renin A and showed similar pressor response activity with 20 ng quantities of the purified proteins. The closely related characteristics of these five forms of renin were further demonstrated by their similarity in peptide mapping patterns after limited digestion with Staphylococcus aureus V8 protease. The data suggest that these proteins are homologous proteins.

Animals↗
PubMed1982

Relationship of specific granules to renin activity in the myocardium.

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. Although this renin activity was partially abolished by preincubation with specific antiserum, the present results do not rule out the possibility that the activity is due to cathepsin D.

Animals↗
PubMed1982

Effect of sodium intake on biosynthesis of renin.

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. The radioactivity incorporated into the renin was 0.07 to 0.22% of that found in the soluble protein. The radioactivity incorporated into renin was increased with incubation time at nearly linear rate and it was decreased by the addition of puromycin or of large amount of unlabeled leucine into the incubation medium. The specific activities of radioactive renin in slices from both mice fed a low sodium and high sodium diet were the same. However, the total radioactivity in renin of the slices from mice fed with low sodium diet was higher than that from mice fed with high sodium diet. This indicates that the production of renin in the mice on low sodium diet was accelerated as compared to that in mice on high sodium diet. The results suggest that change of sodium balance affects the biosynthesis of renin which can lead to changes of renal renin content and its release from the kidney.

Animals↗
PubMed1981

Prostaglandins and renin release in vitro.

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). Our results showed that AA at 1.5 X 10(-8) M significantly increased renin release at 10 and 30 min of incubation. This renin increase ws abolished by either ETA or indomethacin. Prostaglandin F2 alpha (PGF2 alpha) also significantly stimulated renin release at 10 and 60 min. PGE2 and 16,16-dimethyl PGE2 (DMPGE2) showed much less renin release-stimulating activity. EPA and PGI2 on the other hand very strongly stimulated renin release. However, at higher concentrations the stimulating effect of PGI2 and EPA disappeared and even became inhibitory in the case of EPA. Other prostaglandins were found to have no effect on renin release. The results suggest that the prostaglandin system directly affects renin release from the juxtaglomerular cells independent of systemic neurogenic and hemodynamic influences.

Animals↗