Thromboxane and prostacyclin metabolites in pulmonary hypertension.
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Endothelins↗
Biomedical subjects
A Carayon
Publications and source records attributed to A Carayon.
[Atrial natriuretic factor in heart insufficiency].
The atrial natriuretic factor is a peptide with vasodilator and natriuretic properties which is synthesized and released by atrial myocytes. In patients with chronic heart failure the ventricles contribute to the synthesis of this peptide, so that its plasma concentration rises in proportion to the heart filling pressure. The atrial natriuretic factor, therefore, seems to be a good biological marker of functional and haemodynamic severity of heart failure. However, the weight of this factor in the neuro-hormonal balance has not yet been fully evaluated, owing to the usual attenuation of its biological effects. This, and the necessity of continuous parenteral administration limits, for the moment, its therapeutic applications. Inhibitors of the enzyme involved in its metabolism are being tested, but only preliminary results are available in humans.
Atrial Natriuretic Factor↗
Atrial natriuretic peptide during water deprivation or hemorrhage in rats. Relationship with arginine vasopressin and osmolarity.
The concentrations of atrial natriuretic peptide (ANP) in atria, hypothalami and plasma were investigated in relation to the variations of the plasma endogenous immunoreactive arginine vasopressin (Ir-AVP) during water deprivation or hemorrhage in normal conscious Wistar rats. Furthermore, the in vitro and in vivo effect of extracellular hyperosmolarity on ANP release from right atrium and hypothalamus was examined. Water deprivation elevated circulating immunoreactive ANP (Ir-ANP: pg/ml) to 153 +/- 7 (24 h); 174 +/- 1 (48 h) from the control level (109.6 +/- 7.8). This increase in Ir-ANP concentration which correlated with atrial (r = -0.93) or hypothalamic (r = -0.87) Ir-ANP content decrease, was associated with significantly enhanced levels of plasma Ir-AVP, plasma sodium, osmolarity and hematocrit. An acute volume depletion by hemorrhage significantly reduced plasma Ir-ANP (67 +/- 8.4 pg/ml) from the sham operated level (140 +/- 18 pg/ml). Plasma Ir-AVP was elevated dramatically (207.4 +/- 53.4 pg/ml) compared with the sham operated level (8.8 +/- 2.6 pg/ml). These results, indicating the lack of correlation between plasma Ir-ANP and Ir-AVP in vivo, suggest that the ANP secretion, which is regulated mainly by plasma volume, may be modulated by a change in plasma osmolarity. Extracellular hyperosmolarity stimulated the ANP release from superfused sliced normal rat atria and hypothalami.
Animals↗
Plasma calcitonin gene-related peptide decreases in chronic congestive heart failure.
To investigate the role of calcitonin gene-related peptide (CGRP) in cardiac failure, a sensitive and specific radioimmunoassay was developed to study plasma levels of CGRP in 37 normal subjects and 41 patients with heart failure (HF). The mean plasma levels of CGRP were 294.3 pg.ml-1 (SEM: 41.4) in normal subjects and 121.2 pg.ml-1 (SEM: 21.2) in HF patients. The significant decrease observed in HF patients suggests that CGRP is involved in the pathogenesis of heart failure via a direct effect or via modulation of sympathetic nervous activity.
Calcitonin Gene-Related Peptide↗
Endothelin in chronic renal failure.
The aims of the present study were to determine plasma endothelin (ET) in chronically uraemic patients, the renal clearance of endogenous ET in normal dog and man, and the effect of acute volaemic expansion on ET. The mean plasma ET concentration in haemodialysis patients was 57.5 +/- 5 pg/ml before haemodialysis and remained unchanged at 52.5 +/- 5 pg/ml after haemodialysis. They were thus significantly elevated both before and after haemodialysis (P less than 0.01) compared with plasma ET in normal subjects of 20.8 +/- 0.8 pg/ml. There was no evidence of ET clearance across the cuprophane membrane of the dialyser. Resting plasma ET values in the 15 non-dialysed uraemic patients ranged between 20 and 52.5 pg/ml (mean 38.2 +/- 2.3 pg/ml), significantly greater than those observed in controls (P less than 0.01). In CAPD patients, plasma ET was also significantly (P less than 0.01), elevated (63 +/- 10 pg/ml) when compared to controls, and similar to those observed in patients before haemodialysis. In dogs, mean ET did not diminish between the aorta and the renal vein (28.1 +/- 1 versus 28.4 +/- 2 pg/ml). In man mean ET did not significantly decline between the renal artery and the renal vein (17 +/- 3 to 13 +/- 0.8 pg/ml). In the seven healthy subjects who received 2000 ml of isotonic saline intravenously ET remained unchanged (24 +/- 2; 23 +/- 1 and 23 +/- 2 pg/ml before and 1 and 2 h after starting hydration respectively). We have thus shown that plasma ET is elevated in patients with chronic renal failure especially those on dialysis and CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Plasma endothelin-1 concentrations in polyarteritis nodosa.
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Endothelins↗
[Atrial natriuretic factor and cardiac insufficiency].
The atrial natriuretic factor (ANF) is a vasodilating and natriuretic peptide. In experimental and human cardiac failure, plasma ANF concentrations are increased. The ANF is a good marker of functional and haemodynamic severity and of the prognosis of cardiac failure. In this syndrome, messenger RNA of ANF is expressed not only in the atria but also in the ventricles which also secrete the peptide. Attenuation of the natriuretic response is observed in cardiac failure. It may be related to an abnormality situated after the receptor and second messenger, cyclic GMP and/or the reduction of renal perfusion pressure which occurs in cardiac failure. The therapeutic perspectives of ANF in cardiac failure are limited by the necessity of continuous intravenous or parenteral administration. Inhibitors of the enzyme degrading the peptide, neutral endopeptidase, are under evaluation in clinical trials which are at a preliminary stage for the moment.
Atrial Natriuretic Factor↗
Effects of arginine vasopressin and extracellular osmolarity on atrial natriuretic peptide release by superfused rat atria.
This study investigated the characteristics of atrial natriuretic peptide (ANP) release from superfused sliced atria and ventricles of rats. Right atria spontaneously released more immunoreactive ANP (Ir-ANP: pg/min per mg tissue) (32 +/- 3) than did left atria (11 +/- 2) or right ventricles (1.5 +/- 0.5). Addition of 10(-9) to 10(-5) M of arginine vasopressin (AVP) to the superfusing fluid or increasing its osmolarity (290 to 490 mOsM) resulted in a significant increase of the Ir-ANP outflow from right atria. The effect of AVP was prevented by a specific V1 receptor antagonist, ([d(ch2)5Tyr(Me)]AVP). Superfusion with indomethacin (10(-5) M) did not alter spontaneous release but inhibited the peak levels of Ir-ANP induced by AVP (10(-5) M). Moreover, DDAVP, a specific V2 receptor agonist, did not induce Ir-ANP release. Ca(2+)-free medium alone or plus 1 mM EGTA induced a significant increase in basal Ir-ANP outflow. The Ir-ANP released chromatographed similarly to the standard alpha-rANP. These results suggest a specific stimulatory effect of AVP and osmolarity and a negative influence of extracellular Ca2+ on atrial spontaneous Ir-ANP release. It appears that the effect of AVP could be mediated by prostaglandin synthesis.
Animals↗
Increased endothelin level after cyclosporine therapy.
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Adult↗
Low molecular weight hydroxyethyl starch 6% compared to albumin 4% during intentional hemodilution.
Intentional normovolemic hemodilution was chosen as the model to compare a 6% low molecular weight hydroxyethyl starch (LMW HES) to 4% albumin. The study ran over the plasma exchange period for 24 h. Nine patients, scheduled for abdominal aortic surgery, were included in each group. After basal measurements, blood was withdrawn and simultaneously replaced by either 4% albumin (Group 1) or 6% LMW HES (Group 2) to achieve a final hematocrit of approximately 30%. Hemodynamic blood oxygen gas and hormonal plasma levels were determined before hemodilution then at 30 min, 1, 2, 3, and 24 h after the end of hemodilution. Basal value for total blood volume was 4377 +/- 162 ml in group 1 and 4138 +/- 315 ml in group 2. As in both groups the decrease in blood cell volume was exactly compensated by the increase in plasma volume, no significant change in total blood volume (respectively 4432 +/- 159 and 4305 +/- 267 ml) was observed. Throughout the study, in both groups, no significant change in mean arterial and right atrial pressures was observed. In group 2 (LMW HES), a significant increase of pulmonary capillary wedge pressure was noted 120 min after hemodilution. After hemodilution, despite a significant decrease in arterial oxygen O2 content, systemic oxygen transport did not significantly vary until 24 h in relation to the increased cardiac index. An increase in O2 extraction was observed after the exchange but no further increase was observed until the 24 h. No significant changes either in global O2 consumption or in lactate concentration were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia.
Levels of iron, copper, zinc and manganese were measured by inductively coupled plasma spectroscopy in frozen postmortem brain tissue from patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy with strionigral degeneration (MSA), and Huntington's disease (HD) compared with control subjects. Total iron levels were found to be elevated in the areas of basal ganglia showing pathological change in these disorders. In particular, total iron content was increased in substantia nigra in PD, PSP and MSA, but not in HD. Total iron levels in the striatum (putamen and/or caudate nucleus) were increased in PSP, MSA and HD but not in PD. Total iron levels were decreased in the globus pallidus in PD. There were no consistent alterations of manganese levels in basal ganglia structures in any of the diseases studied. Copper levels were decreased in the substantia nigra in PD, and in the cerebellum in PSP, and were elevated in the putamen and possibly substantia nigra in HD. Zinc levels were only increased in PD, in substantia nigra and in caudate nucleus and lateral putamen. Levels of the iron binding protein ferritin were measured in the same patient groups using a radio-immunoassay technique. Increased iron levels in basal ganglia were generally associated with normal or elevated levels of ferritin immunoreactivity, for example, the substantia nigra in PSP and possibly MSA, and in putamen in MSA. The exception was PD where there was a generalized reduction in brain ferritin immunoreactivity, even in the substantia nigra. An increase in total iron content appears to be a response to neurodegeneration in affected basal ganglia regions in a number of movement disorders. However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. These findings suggest an alteration of iron handling in the substantia nigra in PD. Depending on the form in which the excess iron load exists in nigra in PD, it may contribute to the neurodegenerative process.
Aging↗
[Progression towards dislocations of foot bone lesions in leprosy].
From a series of 211 tarsal, medio-tarsal and metatarso-phalangeal dislocations, the authors, after having recalled the lesion mechanism, adopted a classification and gave a place to preventive conservative surgery in 52 cases. The early forms can have early limited arthrodesia. The developed lesions present indications of arthrodesia--isolated reconstruction or associated to spongy or cortico-spongy bone grafts. The late forms impose amputation even when the forefoot seems of good bone quality because the metatarsal-phalangial stiffness is the cause for the failure of the Wladimiroff-Mickulicz interventions.
Amputation, Surgical↗
[A practical note on the early diagnosis of neuritis of the median and ulnar nerves].
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Humans↗
Beta-adrenoceptor blockade potentiates exercise-induced release of atrial natriuretic peptide.
The effect of a non selective and a cardio-selective beta-blocker on basal and exercise-stimulated plasma atrial natriuretic peptide concentrations in healthy volunteers has been studied. Nine healthy volunteers received single oral doses of 5 mg tertatolol, 100 mg atenolol or placebo, at one week intervals, in a double blind cross over trial. At rest plasma atrial natriuretic peptide, aldosterone, antidiuretic hormone and cyclic GMP concentrations and plasma renin activity were not modified by the treatments. During exercise plasma atrial natriuretic peptide concentrations were significantly increased by each treatment, the increment being significantly greater on beta-blockers than on placebo. The rise in atrial natriuretic peptide was 72% after placebo (from 24 to 42 pg/ml), 184% after atenolol (from 30 to 86 pg/ml), and 183% after tertatolol (from 34 to 95 pg/ml), respectively. Thus, the study has shown that in healthy subjects the plasma natriuretic peptide concentration is increased by exercise and that the increase is considerably and equally potentiated by selective and non selective beta-adrenoceptor blockade. The effect may be mainly due to a reduction in ventricular contractility with an increase in atrial pressure. The beta-blockers did not influence the resting plasma atrial natriuretic peptide levels, which suggests that in healthy subjects basal atrial natriuretic peptide secretion is not controlled via beta-receptors.
Adrenergic beta-Antagonists↗
Regional distribution of calcitonin gene-related peptide-, substance P-, cholecystokinin-, Met5-enkephalin-, and dynorphin A (1-8)-like materials in the spinal cord and dorsal root ganglia of adult rats: effects of dorsal rhizotomy and neonatal capsaicin.
Biochemical mapping of five different peptide-like materials--calcitonin gene-related peptide (CGRP), substance P (SP), Met5-enkephalin (ME), cholecystokinin (CCK), and dynorphin A (1-8) (DYN)--was conducted in the dorsal and ventral zones of the spinal cord at the cervical, thoracic, and lumbar levels in 3-month-old rats 10 days after unilateral dorsal rhizotomy at the cervical level (C4-T2) or after neonatal administration of capsaicin (50 mg/kg s.c.). In control rats, all peptide-like materials were more abundant in the dorsal than in the ventral zone all along the spinal cord. However, in both zones, absolute concentrations of CGRP, SP, ME, and CCK were significantly higher at the lumbar than at the cervical level. Rhizotomy-induced CGRP depletion (-85%) within the ipsilateral dorsal zone of the cervical cord was more pronounced than that due to neonatal capsaicin (-60%), a finding suggesting that this peptide is contained in both capsaicin-sensitive (mostly unmyelinated) and -insensitive (myelinated) primary afferent fibers. In contrast, similar depletions of SP (-50%) were observed after dorsal rhizotomy and neonatal capsaicin treatment, as expected from the presence of SP only in the capsaicin-sensitive small-diameter primary afferent fibers. Although the other three peptides remained unaffected all along the cord by either intervention, evidence for the existence of capsaicin-insensitive CCKergic primary afferent fibers could be inferred from the increased accumulation of CCK (together with SP and CGRP) in dorsal root ganglia ipsilateral to dorsal root sections.
Afferent Pathways↗
Decreased ferritin levels in brain in Parkinson's disease.
Ferritin levels were measured in postmortem brain tissue from patients dying with Parkinson's disease [treated with L-3,4-dihydroxyphenylalanine (L-DOPA)] and from control patients. Ferritin levels were decreased in the substantia nigra, caudate-putamen, globus pallidus, cerebral cortex, and cerebellum when compared with age-matched control tissues. However, in CSF from L-DOPA-treated patients and in serum from L-DOPA-treated and untreated parkinsonian patients, ferritin levels were normal. Previous studies have suggested an increased total iron content in substantia nigra of parkinsonian brain. The failure of substantia nigra ferritin formation to be stimulated by increased iron levels suggests some defect in iron handling in this critical brain region in Parkinson's disease. The reason for decreased ferritin levels throughout the parkinsonian brain is not clear but does not seem to reflect a general system deficit in ferritin.
Brain Chemistry↗
Plasma concentration of atrial natriuretic hormone during endogenous glucocorticoid hypercorticism.
In vitro studies have shown that glucocorticoids may increase atrial natriuretic-hormone (ANH) synthesis and/or release. This action of glucocorticoids has also been suggested in vivo in patients with Cushing's syndrome. However, in this circumstance, plasma AH elevation might be due to humoral disturbances associated with cortisol overproduction. We studied 16 patients with endogenous hypercorticism and 11 of them after successful treatment. Plasma levels of ANH, plasma renin activity (PRA), aldosterone, desoxycorticosterone (DOC), angiotensin II (AII), cortisol, osmolarity, sodium and potassium, urinary free cortisol (UFC), and blood pressure were measured. Before treatment the mean plasma ANH concentration in patients with Cushing's syndrome was significantly higher than in controls (11.3 +/- 2.6 vs. 4.9 +/- 2.3 pmol/l; p less than 0.001). ANH was correlated with cortisol and UFC (r = 0.715, r = 0.700; p less than 0.05). There was no significant correlation between plasma ANH, PRA, aldosterone, DOC, AII, osmolarity, sodium or blood pressure. After recovery, ANH concentration decreased in all patients and was not different from that of normal subjects (4.9 +/- 2.3 vs. 4.3 +/- 2.6 pmol/l). These results suggest that in Cushing's syndrome, ANH secretion is mainly dependent on the severity of hypercortisolism and independent of the other associated disturbances that we studied.
ACTH Syndrome, Ectopic↗
Renal and hemodialysis clearances of endogenous natriuretic peptide. A clinical and experimental study.
The purpose of the present study was to assess the plasma levels of atrial natriuretic peptide (ANP) in chronically uremic patients not submitted to dialysis and to determine the predialysis plasma concentration of ANP, the effect of ultrafiltration on plasma levels of ANP (hemodialysis, (HD), and the HD clearance of ANP in a population of adult patients treated with maintenance HD. The mean plasma ANP concentration (pg/ml) in HD was 370.2 +/- 35.5 pg/ml (mean +/- SEM) before HD and decreased to 165.3 +/- 15.2 after HD (p less than 0.01). Both values were significantly higher than in controls (28 +/- 2; n = 39). The changes in plasma ANP levels correlated inversely with those in plasma protein concentration (r = -0.53; p less than 0.03; y = 48.6 +/- 0.8 x). ANP clearance across the cuprophan membrane averaged 13 +/- 6.4 ml/mn. Resting plasma ANP values in the 16 uremic patients ranged between 16 and 277 pg/ml (124 +/- 11 pg/ml). These levels were significantly higher than those observed in controls (p less than 0.01). In these patients there was a highly significant correlation between serum creatinine and plasma ANP concentrations (p less than 0.01; r = 0.75; y = 0.2x + 3). Furthermore we report the results of the determination of the renal clearance of ANP in normal dogs. In all dogs a fall in plasma ANP concentration was recorded between the aorta (28.6 +/- 4.5 pg/ml) and the renal vein (14.2 +/- 2.7 pg/ml). The renal extraction ratio averaged 51.3 +/- 3.7%. Mean ANP renal clearance was 38.2 +/- 5.2 ml/mn.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗