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Biomedical subjects

G Thibault

Publications and source records attributed to G Thibault.

At least 145 records · Page 8Linked to original sources
PubMed1989

Ventricles as a major site of atrial natriuretic factor synthesis and release in cardiomyopathic hamsters with heart failure.

The aim of the present study was to correlate in cardiomyopathic hamsters with congestive heart failure the levels of atrial and ventricular atrial natriuretic factor (ANF) messenger RNA (mRNA) with immunoreactive ANF (IR-ANF) plasma levels and the relative amount of IR-ANF released by the whole heart versus isolated ventricles in the Langendorff preparation. High-performance liquid chromatography analysis of the forms of ANF present in plasma and in the Langendorff effluent of whole heart versus isolated ventricles was also performed. As previously found for cardiac IR-ANF, the levels of ANF mRNA decreased gradually in atria and increased in an analogous fashion in ventricles with the severity of congestive heart failure. Plasma IR-ANF levels (C-terminal) were more elevated in moderate than in severe congestive heart failure, as were the IR-ANF levels in the Langendorff effluent of the whole heart. On the contrary, the effluent of isolated ventricles from animals in severe heart failure yielded more IR-ANF than that from hamsters in moderate heart failure. Thus, while the isolated ventricles from controls contributed 35.8% of IR-ANF released by the whole heart, ventricles from hamsters in moderate heart failure contributed 17.5%, and those from hamsters in severe heart failure contributed 73.9%. These results indicate that atrial cardiocytes contribute more IR-ANF than their ventricular counterpart in moderate heart failure and that ventricles are a major source of plasma IR-ANF in severe heart failure. Analysis of IR-ANF from plasma and the Langendorff effluent from whole hearts and isolated ventricles revealed that the ventricles are the major source of the propeptide (and of its cleaved products) found in the circulation of cardiomyopathic hamsters. These results suggest that ANF synthesis and secretion do not increase conjointly in atria but do increase in ventricles during congestive heart failure.

Animals↗
PubMed1989

Processing of the atrial natriuretic factor propeptide by atrial cardiocytes as revealed by immunocryoultramicrotomy.

Antibodies were raised against three fragments of the rat ANF molecule: C-terminal atrial natriuretic factor (ANF)-(101-126), N-terminal ANF-(11-37), and the putative cleavage site of the ANF propeptide, ANF-(94-103). These antibodies were purified by affinity chromatography and revealed a major band (17K) corresponding to the propeptide by Western blot analysis. Antibodies against ANF-(94-103) were used in a RIA. All of the peptides that possess this region (98-99) were able to displace iodinated pro-ANF from the antibody. However, peptides that have only one part of the fragment, such as ANF-(99-126) or ANF-(1-98), failed to displace pro-ANF; human ANF-(79-98) (100 pmol) demonstrated about 0.01% cross-reactivity. Immunohistochemical studies revealed that all atrial cardiocytes are reactive with the three antibodies. Immunocryoultramicrotomy revealed that the propeptide travels, uncleaved, from the Golgi complex to immature granules and mature secretory granules. These results indicate that cleavage of the ANF propeptide does not occur at these sites.

Animals↗
PubMed1989

Physiological levels of immunoreactive ANH-like peptides in human follicular fluid.

The concentrations of immunoreactive C-terminal (ANH-(99-126)) and N-terminal (ANH-(1-98] portions of pro-ANH were measured in follicular fluid and plasma samples from 9 young women undergoing in vitro fertilization. ANH-(99-126) and ANH-(1-98)-like immunoreactivity levels in plasma were 6.0-25.4 (mean 12.2 pmol/l and 184-427 (mean 300) pmol/l, respectively, whereas the corresponding levels in follicular fluid were 3.8-8.0 (mean 4.9) pmol/l and 169-385 (mean 262) pmol/l. The concentrations of both ANH-like peptides were consistently lower (p less than 0.01) in the follicular fluid than in the matched plasma samples, but within the variation found in plasma controls. It is concluded that ANH-like peptides in the follicular fluid, whether secreted locally or derived from circulating ANH, might play a physiological role in the biosynthesis of ovarian steroid hormones or follicular maturation and fluid dynamics.

Atrial Natriuretic Factor↗
PubMed1989

Echocardiographic measurements and plasma levels of atrial natriuretic factor.

Atrial distension and pressure have been reported to be important for the release of atrial natriuretic factor (ANF) into the circulation. However, in mild essential hypertension, we have been unable to demonstrate an increase in plasma levels of ANF. To evaluate more precisely the lack of increase of ANF, we measured echocardiographically the diameters of the cardiac chambers and correlated these measurements with ANF values in normal subjects (n = 25), in patients with untreated essential hypertension (n = 20), and in patients with treated essential hypertension (n x 27). The plasma values of ANF were 21.9 +/- 2.8 pg/ml in the normal controls, 20.4 +/- 2.2 pg/ml in patients with untreated mild essential hypertension, and 32.6 +/- 2.8 pg/ml in patients with treated but uncontrolled essential hypertension (p less than 0.05). The plasma values of cGMP were 4.53 +/- 0.56 pmol/ml in the normal, 5.41 +/- 0.57 pmol/min in the patients with untreated essential hypertension, and 6.76 +/- 0.58 pmol/ml in treated essential hypertension (p less than 0.05). There were no significant differences in the size of the cardiac chambers between the three groups, except for the size of the right atrium, but there was a correlation between the ANF values and the size of the left atria (r = 0.29, p = 0.01, n = 72), as well as with the size of the intraventricular septum (IVS) in systole (r = 0.36, p = 0.002, n = 72). Since ANF levels are similar in mild untreated essential hypertension and normal volunteers, the ANF plasma levels could be a better reflection of the impact of the blood pressure on the myocardium than the level of blood pressure itself and indicate in patients the degree of cardiac impairment. On the other hand, there seems to be definitely an effect of treatment on the levels of ANF.

Adult↗
PubMed1989

Intramuscular and subcutaneous administration of atrial natriuretic factor in the rat.

The effects of ANF (99-126) and its active analog, [3-mercaptopropionic 105]-ANF (105-126), on diuresis and natriuresis were assessed in the rat after intramuscular (i.m.) or subcutaneous (s.c.) injection. Water and sodium excretion increased significantly after i.m. or s.c. administration of either peptide in the first 20-min urine collection. ANF (99-126) was more active i.m. than its analog, while they both produced similar diuresis and natriuresis when they were administered s.c. The rapid and significant increase of plasma IR-ANF levels, detected by radioimmunoassay and analyzed by high performance liquid chromatography after i.m. or s.c. injection of these peptides, indicates very rapid passage into the blood circulation without degradation. These data demonstrate that either the i.m. or s.c. route can be used to administer ANF or its analog.

Animals↗
PubMed1989

Effect of a chronic infusion of atrial natriuretic factor on glomerular and vascular receptors in spontaneously hypertensive rats.

To investigate the effect of a prolonged infusion of atrial natriuretic factor (ANF) on its vascular and glomerular receptors, ANF (Ser 99-Tyr 126) was chronically administered (100 ng/h) for 7 days by osmotic minipumps to spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Blood pressure in the SHR fell from 149 +/- 5 to 119 +/- 3 mmHg 5 days after the ANF infusion was initiated, whereas no changes were observed in ANF-infused WKY rats. The SHR had higher plasma levels of both ANF (1-98) and (99-126) than the normotensive controls, but the ANF infusion did not modify these values in either group. Diuresis, natriuresis and haematocrit remained unchanged during the infusion. The higher plasma ANF levels noted in the SHR were associated with a decreased density (Bmax) and enhanced affinity (Kd) of ANF-binding sites in the mesenteric vessels. This pattern was not modified by the ANF infusion. The hypertensive animals had glomerular ANF receptors with a higher affinity than the WKY rats. The Bmax of these receptors was decreased significantly in ANF-infused SHR and WKY rats compared with non-infused animals. We conclude that the lack of change in vascular ANF receptors, during chronic ANF infusion in the SHR, could be associated with the hypotensive response.

Animals↗
PubMed1989

Cardiovascular, renal and endocrine responses to low doses of atrial natriuretic factor in mild essential hypertension.

The purpose of this study was to evaluate the cardiovascular, renal and endocrine effects of human atrial natriuretic factor (ANF), infused at a rate of 0.8 microgram/min (about 4 pmol/kg/min) for three hours in normal subjects and patients with essential hypertension. This infusion rate was chosen to obtain a range of plasma ANF levels which can be generated by physiological manoeuvres and to reduce the likelihood of hypotension. Five patients and six healthy volunteers participated in the study. The infusion had to be prematurely discontinued in one patient and in one control because of hypotension with relative bradycardia. Blood pressure otherwise remained unchanged during infusion whereas heart rate rose transiently. Plasma ANF levels increased similarly during infusion from 8.9 +/- 2.6 to 23.9 +/- 6.4 pmol/l in patients and from 3.7 +/- 0.7 to 25.4 +/- 6.9 pmol/l in the controls, remained stable during the infusion, and decreased similarly in both groups after the infusion, with a half-life of 7 min. Plasma guanosine cyclic phosphate (cGMP) was augmented by about four-fold in both groups. In both groups, plasma aldosterone levels fell whereas plasma noradrenaline increased. The diuretic effect of ANF was similar in both controls and patients (1354 +/- 161 vs 1542 +/- 116 ml/3 hrs respectively), whereas its natriuretic effect was exaggerated in hypertensive patients (90 +/- 11 vs 62 +/- 9 mmol/3 hrs, P less than 0.05). In conclusion, this low infusion rate of ANF produced similar changes in plasma ANF, cGMP, aldosterone and noradrenaline levels but patients with mild essential hypertension demonstrated an exaggerated diuretic and natriuretic response to ANF infusion.

Adult↗
PubMed1988

Contribution of blood and systemic circulation to the processing of pro-(atrial natriuretic factor).

Atrial natriuretic factor-(Asn1-Tyr126)-peptide, the 13.6 kDa propeptide of atrial natriuretic factor (ANF), is stored in the secretory granules of atrial cardiocytes. ANF-(Ser99-Tyr126)-peptide, the 28-amino-acid species, is the circulating form of this hormone in the rat. As the site of maturation of the prohormone is still unknown, the present study was undertaken to understand the contribution of the circulation to the maturation process of pro-ANF. 125I-ANF-(Asn1-Tyr126)-peptide was incubated with whole rat blood, plasma or serum for different time intervals, and the products were analysed. There was minimal activation of the propeptide in either whole blood or plasma. Incubation with serum, however, resulted in the formation of an 11 kDa and a 3 kDa peptide which corresponded respectively to the N-terminal and C-terminal parts of the propeptide. These results suggest that hydrolysis of the propeptide in serum is brought about by enzymes that may be stimulated during coagulation but which may not play a major role in the activation of pro-ANF in the circulation. Plasma analysis at different time intervals after prohormone injection indicated a non-specific hydrolysis of the pro-ANF molecule. The disappearance rate curves, obtained with radiolabelled pro-ANF, suggested the presence of two components with half-lives of 2.1 +/- 0.4 min and 52.5 +/- 8.4 min respectively. A metabolic clearance rate of 1.49 +/- 0.22 ml/min and an initial distribution volume of 47.4 +/- 8 ml were calculated. These results indicate that the maturation of pro-ANF to its active circulating form takes place before it is released into the circulation.

Animals↗
PubMed1988

Radioreceptor assay for atrial natriuretic factor.

Interest in accurate measurement of atrial natriuretic factor (ANF) in biological fluids and various tissues has been stimulated by recent data indicating the possible role of ANF in the homeostasis of salt and water. The presence of high-affinity binding sites for ANF in rat glomeruli has allowed us to develop a rapid, sensitive, and simple radioreceptor assay (RRA). A saturable high-affinity binding site on the membranes of rat glomeruli has been characterized by a dissociation constant of 33 pM and binding capacity of 396 fmol/mg protein. Rat plasma extracts or atrial homogenates or standards were incubated with radioiodinated ANF and a preparation of rat glomerular membranes. The receptor-bound and free radioactivity were separated by filtration on Whatman GF/C paper after 1 h incubation at room temperature. The sensitivity of the RRA was 2.08 fmol. The effective concentration of standard ANF that displaced 50% of labeled receptor-bound ANF (EC50) was 43.3 +/- 2.6 fmol/ml (n = 7). Both intra- and interassay coefficients of variation were smaller than 11%. This RRA assay has been compared with radioimmunoassay (RIA). High correlations for 19 plasma extracts and 34 atrial homogenates (r = 0.973 and r = 0.954, respectively) tested by RRA and RIA were obtained. This good correlation between the two methods suggests that the immunoreactive material found in rat plasma and atrial homogenates also displays biological activity.

Animals↗
PubMed1988

Atrial natriuretic factor in experimental and human hypertension.

Plasma levels of immunoreactive atrial natriuretic factor (IR-ANF) were evaluated by radioimmunoassay in several models of experimental hypertension and in human hypertension. Plasma levels of IR-ANF are consistently increased in all models of experimental hypertension studied so far. This is accompanied by a decrease of IR-ANF levels in the left atrium at certain times. Plasma levels of IR-ANF are not increased in human essential hypertension, except in the severe form (diastolic blood pressure above 110 mmHg). Peripheral levels of IR-ANF in renovascular hypertension do not differ from normal but are increased above normal in aortic blood.

Animals↗
PubMed1988

Glomerular ANF receptor regulation during changes in sodium and water metabolism.

The concentration of atrial natriuretic factor (ANF) in atria and plasma was investigated in relation to the regulation of renal glomerular ANF receptors in the rat during changes in water and sodium intake. A decrease in plasma immunoreactive ANF (IR-ANF) was observed after 4 days of water deprivation or after 1 wk on a low-sodium diet, whereas animals offered 1% NaCl in their drinking water had elevated plasma ANF values. Atrial IR-ANF was lower in water-deprived and higher in sodium-restricted rats than in their respective controls. A low-sodium intake or water deprivation increased the density of glomerular ANF receptors, whereas the inverse occurred with a high-salt consumption. It is concluded that an inverse correlation exists between ANF plasma concentration and renal glomerular ANF receptor sites.

Animals↗
PubMed1988

Glomerular atrial natriuretic factor receptors during rehydration: plasma NH2- and COOH-terminal levels.

Atrial natriuretic factor (ANF) concentration in atria and plasma was investigated in relation to the density and affinity of renal glomerular ANF receptors during water deprivation and rehydration in the rat. Immunoreactive (IR) ANF-(99-126) was lower during water deprivation (4.2 +/- 0.5 fmol/ml) than in normally hydrated animals (10 +/- 1.5 fmol/ml); NH2-terminal IR ANF-(1-98) was also lower in water-deprived rats (75 +/- 2.4 fmol/ml) than in the controls (708 +/- 105 fmol/ml). These decreased plasma COOH- and NH2-terminal ANF concentrations were accompanied by significantly higher hematocrit, serum osmolality, and Na+ values. The renal glomerular ANF receptor population was greater in water-deprived animals than a control animals. After rehydration, IR ANF was elevated within 1 h and reached control values after 6 h. Hematocrit, serum osmolality, and Na+ did not normalize until 48, 6, and 24 h, respectively. The renal glomerular ANF receptor population, which was markedly higher in water-deprived rats, gradually declined after rehydration, so that no difference was observed with the control group 24 h later.

Animals↗
PubMed1988

Identification and plasma concentrations of the N-terminal fragment of proatrial natriuretic factor in man.

A specific RIA was developed to measure plasma atrial natriuretic factor (ANF) N-terminal immunoreactivity in man. Antibodies raised in rabbits against a rat ANF N-terminal fragment [ANF-(11-37)] had 100% cross-reactivity with human ANF-(1-30) and purified plasma N-terminal ANF immunoreactivity. The ED80 and ED50 of standard curves prepared using [125I]human ANF-(1-30) and human ANF-(1-30) were 31.5 +/- 5.4 (+/- SD) and 132.5 +/- 20.4 fmol/tube, respectively. The plasma ANF N-terminal peptide concentrations were assayed directly, without extraction, since dilution of plasma and addition of standard to plasma yielded parallel dose-responses in the RIA and virtually 100% recovery of ANF-(1-30) added to plasma. Purification of ANF N-terminal immunoreactivity from 1.5 L human plasma by affinity chromatography and amino acid sequencing suggested that it was closely related to ANF-(1-98), although some degraded peptides were also detected. The mean basal plasma ANF N-terminal peptide level measured in 34 normal subjects was 420 +/- 157 (+/- SD) pmol/L. The values were higher in plasma from patients with congestive heart failure (grades III and IV; 7,041 +/- 6,136 pmol/L; n = 13) or chronic renal failure (10,079 +/- 4,942 pmol/L; n = 20). In 9 patients with chronic renal failure, hemodialysis resulted in a 30% (P less than 0.05) decrease in plasma ANF-(99-126) levels, from 34.7 +/- 12.3 (+/- SD) to 23.2 + 6.1 pmol/L, but no changes in plasma ANF N-terminal peptide concentrations. These data indicate that the N-terminal portion of pro-ANF is cosecreted with ANF-(99-126). Its higher plasma levels in the basal state and during chronic renal failure suggest a different process of elimination than that of ANF-(99-126), which may be partly mediated by the kidney.

Adult↗
PubMed1988

ANF in experimental congestive heart failure.

The plasma and cardiac levels of immunoreactive (IR) atrial natriuretic factor (ANF) were measured during the entire lifespan of cardiomyopathic hamsters, which eventually develop spontaneous congestive heart failure, and were correlated with immunohistochemical, ultrastructural, and immunocytochemical changes in the secretory apparatus of atrial and ventricular cardiocytes. Plasma IR-ANF rose in the early stages of the disease, reached a maximum in moderate heart failure, and declined thereafter but remained above control values. The peptide decreased constantly in the atria during the evolution of the disease but increased markedly in the ventricles. Its highest levels were found in the inner half of the left ventricle. In atrial cardiocytes, the size and complexity of the Golgi complex increased with the progression of the disease, whereas the number, size, and IR-ANF content (as assessed by the immunogold technique) of secretory granules decreased constantly. In ventricular cardiocytes, the size of the Golgi complex increased, and typical secretory granules were present in approximately 20% of these cells, regardless of their localization in the myocardium. The results suggest that stimulation of ANF secretion in atrial cardiocytes leads to a dissociation between synthesis and release, the latter being maximal according to ultrastructural and immunocytochemical criteria. In ventricular cardiocytes, the same stimulation culminates in increased synthesis and the possibility of release via two pathways: one constitutive, the other regulated. Thus, the elevated plasma levels of IR-ANF in congestive heart failure may be derived from secretion by both atrial and ventricular cardiocytes.

Animals↗
PubMed1988

[Effects of phenylephrine on atrial natriuretic factor and the renin-aldosterone axis in normal patients and essential hypertensive patients].

Phenylephrine infusions enhance diuresis and natriuresis both in normal subjects and patients with essential hypertension, whereas they have an opposite effect on urinary aldosterone excretion, decreasing it in normal subjects and enhancing it in hypertensive patients. With the new knowledge concerning the atrial natriuretic factor (ANF), it seemed a strong possibility that in normal subjects phenylephrine infusions should exert its effect through the increased release of ANF, as suggested by in vitro studies. Phenylephrine infusions at high pressor dose (to increase diastolic pressure by 25 mmHg) in six healthy volunteers increased plasma ANF and cGMP and decreased plasma renin activity and aldosterone concentrations. Urinary volume, sodium, and cGMP excretion were also increased. Phenylephrine infusions at low pressor dose (to increase diastolic pressure by 12-15 mmHg), in healthy subjects and in five patients with mild essential hypertension, significantly increased plasma ANF concentrations and decreased plasma renin activity to the same degree in both groups. But, whereas in normal subjects plasma aldosterone decreased significantly, it increased in patients with mild essential hypertension despite the simultaneous rise in plasma ANF concentration.

Adult↗
PubMed1988

Ganglionic, spinal cord and hypothalamic atrial natriuretic factor: its distribution, origin and possible role in spontaneously hypertensive rats.

We report the occurrence of the atrial natriuretic factor (ANF) prohormone in the hypothalamus, spinal cord and sympathetic ganglia determined by measurement of immunoreactive ANF by two peptide-specific radio-immunoassays with antibodies against near-C-terminal and near-N-terminal portions of ANF prohormone. This suggests local ANF generation in neural structures. In spontaneously hypertensive rats (SHR) we found an elevated ANF-C content in all tissues along the pathway of increased efferent sympathetic outflow, which is present in this animal model. The ANF-N was augmented in SHR only in the hypothalamus. This indicates an overall increase of neural ANF in SHR. The reported neuroinhibitory function of increased neural ANF, however, was attenuated by a decrease in the number of some brain and peripheral ganglionic ANF binding sites in SHR. It remains to be determined whether the increased neural ANF in SHR is a primary phenomenon or a compensatory increase induced by high blood pressure.

Animals↗
PubMed1987

Correlation between cardiac hypertrophy and plasma levels of atrial natriuretic factor in non-spontaneous models of hypertension in the rat.

We have compared atrial and plasma concentration of atrial natriuretic factor (ANF) in 4 models of non spontaneous experimental hypertension with different pathogenic mechanisms in the rat: two-kidney, one-clip (2-K, 1-C), one-kidney, one-clip (1-K, 1-C), DOCA-NaCl and adrenal regeneration hypertension (ARH) and their respective normotensive controls. All hypertensive groups developed cardiac hypertrophy. In all hypertensive groups plasma ANF was higher than in controls. Atrial ANF concentration was lower in the right and left atrium of 1-K, 1-C rats and in the left atrium of ARH. A good correlation was found between systolic BP and plasma ANF in 2-K, 1-C (r = 0.82; p less than 0.01) and 1-K, 1-C animals (r = 0.70; p less than 0.01). This correlation was less good in DOCA-NaCl (r = 0.41; p less than 0.05) and non existent in ARH (r = 0.28; NS). A negative correlation between plasma ANF and atrial ANF concentrations was found only in the 1-K, 1-C group (r = 0.41; p less than 0.05). A good correlation between plasma ANF levels and cardiac weight was found in all groups: 2-K, 1-C (r = 0.83; p less than 0.01), 1-K, 1-C (r = 0.73; p less than 0.01), DOCA-NaCl (r = 0.69; p less than 0.01) and ARH (r = 0.71; p less than 0.01). We suggest that the release of ANF in experimental hypertension depends of the pathogenesis and could be related either to the level of BP (hence the magnitude of the left ventricular end-diastolic pressure) or to the existence of an expanded blood volume. The correlation between plasma ANF levels and cardiac hypertrophy suggests that ANF could be partially released by the ventricles.

Adrenal Glands↗