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Biomedical subjects

J Genest

Publications and source records attributed to J Genest.

At least 145 records · Page 8Linked to original sources
PubMed1987

Atrial natriuretic factor.

A short and up-to-date review on the great advances made in the field of the atrial natriuretic factor (ANF) is presented. All the short active peptides (up to 33 AA) isolated after purification of atrial homogenates have the same core of 23 amino acids (Ser 103-ARG 125). The ANF liberated in the medium of cultures of rat atrial cardiocytes is the 26 amino acid Arg 101-Tyr 126. Cloning of the cDNA encoding for ANF and of the rat, mouse, and human ANF gene has been accomplished. ANF has a most potent and short-lasting diuretic and natriuretic effect that appears to be predominantly due to a significant increase in glomerular filtration rate. ANF inhibits the release of aldosterone both in vitro and in vivo. It produces a profound inhibition of vascular contraction induced by norepinephrine and angiotensin II. This vasorelaxation is followed by a prolonged refractory period. ANF administration corrects the hypertension in 2K-1C hypertensive rats and in spontaneously hypertensive rats. Specific high-density binding sites have been found in the brain, especially in the hypothalamus, subfornical organ, median eminence, area postrema, and nucleus tractus solitarius, all areas involved in the brain control of hypertension and in the regulation of salt and water. ANF has no effect on the known sodium transport mechanisms across cell membrane. It has a major effect on the stimulation of guanylate cyclase activity, especially in renal glomeruli. Specific radioimmunoassay procedures have been established and results of preliminary studies that establish clearly that ANF is a circulating hormone are presented.

Adrenal Glands↗
PubMed1987

Atrial natriuretic factor--its possible role in the pathogenesis and therapy of arterial hypertension.

Using radioimmunoassay the authors investigated the plasma concentration of the immunoreactive atrial natriuretic factor (IR-ANF) and its content in the atria of 4-, 8-, 12-, 16-, and 20-weeks-old spontaneously hypertensive rats (SHR), and compared the results with data obtained in normotensive Wistar-Kyoto rats of the same age. With hypertension accelerating in SHR between the 8th and the 20th weeks of life, IR-ANF content in the atrium gradually decreased, and the plasma IR-ANF concentration increased. The decline in IR-ANF was due to its decrease primarily in the left atrium. Long-term (6-day) administration of synthetic ANF to SHR with fully developed hypertension led to normalization of BP. The results do not support the hypothesis that arterial hypertension in SHR is induced by a primary deficiency of ANF. The changes in IR-ANF in the atria and plasma occur rather as an adaptive and regulatory response to increasing BP. Prolonged administration of ANF to SHR had a hypotensive effect. Therapeutic application of ANF in man depends on the development of oral and long-acting analogues.

Animals↗
PubMed1987

Influence of hemodialysis on the plasma levels of the atrial natriuretic factor in chronic renal failure.

Atrial natriuretic factor, plasma renin activity, and plasma vasopressin were measured in 38 patients with chronic renal failure prior to and after hemodialysis. The objective of the study was to evaluate the effect of acute volume changes on the level of atrial natriuretic factor. Blood pressure prior to dialysis was 154 +/-/83 +/- mmHg, and 132 +/-/78 +/- mmHg post dialysis (p less than 0.005) while heart rate increased from 82.5 +/- 1.8 beats per minute to 91.2 +/- 2.4 after dialysis (p less than 0.005). The average weight of patients was reduced from 60.2 +/- 2.4 kg to 57.8 +/- 2.4 kg (p less than 0.005). While the plasma levels of atrial natriuretic factor in normal individuals were 65.3 +/- 2.9 pg/ml (n = 59), these levels were 251.4 +/- 28 pg/ml prior to dialysis in the patients with renal failure, and 173.3 +/- 18.0 pg/ml after dialysis (p less than 0.005). Twenty-nine patients had a reduction in the levels of this atrial natriuretic factor, 5 had no change, and 4 had an increase. The atrial factor was not detected in the dialysate fluid of 6 patients in whom it was measured. Peripheral renin values were unchanged from 2.12 +/- 0.68 to 2.07 +/- 0.8 ng/ml/hr. Plasma vasopressin before dialysis was significantly higher than normal, and increased from 7.04 +/- 0.56 to 9.95 +/- 1.55 pg/ml following dialysis (p less than 0.05). The changes in atrial natriuretic factor values correlated most significantly (r = 0.47, p less than 0.005) with the changes in weight, but no single variable could explain the changes in atrial natriuretic factor.

Adult↗
PubMed1987

[Determination of the atrial natriuretic factor in patients with essential and renovascular hypertension].

We have measured the basal circulating level of atrial natriuretic factor (ANF) in hypertensive patients. Plasma ANF concentrations in 101 patients with mild untreated, essential hypertension and in 64 normotensive controls were 14.9 +/- 11.1 vs 11.9 +/- 7.7 pg/ml, p = NS respectively. Plasma ANF levels in the patients were correlated with mean arterial pressure (r = 0.35, p less than 0.001) and age (r = 0.38, p less than 0.001). Sixteen patients with uncontrolled hypertension despite treatment, had significantly higher plasma ANF levels (33.5 +/- 27.3 pg/ml, p less than 0.001). Forty other patients with hypertension were subjected to an abdominal aortography and a renal vein catheterism, in order to rule out renovascular hypertension. Of these subjects, 16 were without significant renal artery stenosis, 12 had left renovascular hypertension and 12 others right renovascular hypertension. Plasma ANF levels were maximal in the aorta and there were no differences between the ANF levels in the renal veins, whether the stenosis was on the right or left side. In conclusion, plasma ANF levels were not elevated in 101 untreated patients with mild essential hypertension. Together with the evidence of elevated intra atrial pressure in mild essential hypertension, as found by others, this suggests that ANF secretion might be impaired in this disease.

Adult↗
PubMed1987

Atrial natriuretic factor (ANF) in experimental and human hypertension.

The plasma levels of immunoreactive (IR)-ANF have been evaluated by radioimmunoassay in several models of experimental hypertension and in human hypertension. In all models of experimental hypertension so far studied, the plasma levels of IR-ANF are consistently increased. This is accompanied by a decrease, at certain time intervals, of the IR-ANF levels in the left atrium. In human essential hypertension, the plasma levels of IR-ANF are not increased except in the severe form (diastolic blood pressure above 110 mmHg). In renovascular hypertension, the peripheral levels of IR-ANF are not different from the normal levels but are increased above normal in aortic blood.

Animals↗
PubMed1986

Degradation of atrial natriuretic factor in the rat.

The biologically active circulating form of atrial natriuretic factor (ANF) in the rat is the 28-amino-acid peptide ANF-(Ser-99-Tyr-126). Degradation of this peptide in vivo as well as in vitro, in whole blood, in plasma and by the isolated mesenteric artery was investigated. Studies in vivo in the rat demonstrated that the elimination and degradation of ANF was extremely fast: within 3 min more than 95% of the injected immunoreactive material was eliminated from circulation. The production of a short C-terminal peptide was detected on injection of 125I-ANF-(Ser-99-Tyr-126) into the rat. This peptide increased proportionately with incubation time. Experiments in vitro in the presence of whole blood or plasma did not cause any major destruction of ANF even after incubation for 60 min. After this prolonged incubation in plasma, ANF-(Ser-99-Tyr-126) was partially converted into ANF-(Ser-103-Tyr-126), a less potent peptide. Isolated mesenteric-artery preparation appeared to degrade ANF in a manner very similar to the system in vivo. These results suggest that degradation of ANF may occur either after internalization in the vascular cells or by a membrane-bound enzyme in the vasculature.

Animals↗
PubMed1986

The morphine effect on plasma ANF.

The effect of acute morphine treatment on plasma immunoreactive atrial natriuretic factor (IR-ANF) was studied in conscious non-hydrated rats. Morphine treatment induced an 8-fold increase in plasma IR-ANF (P less than 0.001) from 68.1 +/- 9.3 (mean +/- S.E.) to 540.5 +/- 139.5 pg/ml and this increase was completely abolished by pretreatment with the opioid antagonist naloxone (P less than 0.001) to 37.9 +/- 2.8 pg/ml. Naloxone also significantly decreased the basal IR-ANF level (P less than 0.05) to 49.0 +/- 5.3 pg/ml. When naloxone-pretreated and control rats were infused with saline (8 ml) the IR-ANF response was the same in the two groups: 257.7 +/- 64 and 247 +/- 52 pg/ml respectively. Since ANF is a potent natriuretic and diuretic hormone, the morphine-induced increase of plasma IR-ANF may provide a rational basis for explaining the diuretic effect of morphine in conscious non-hydrated rats. Moreover, the decrease of basal plasma IR-ANF suggests the possible implication of endogenous opioids in the regulation of basal ANF secretion.

Animals↗
PubMed1986

Atrial natriuretic factor in human plasma.

A reproducible and sensitive radioimmunoassay (RIA) was developed to measure ANF in human plasma. Immunoreactive ANF was extracted from plasma with Sep-Pak cartridges, using 0.2% ammonium acetate (pH 4) with acetonitrile. The sensitivity of the assay was 3.9 pg/ml. The coefficient of variance for inter-assay and intra-assay was 16.8% and 6.8%, respectively. In normal healthy subjects (n = 67), ANF content was 11.9 +/- 1.3 pg/ml (mean +/- SEM). Significantly-higher ANF concentrations were found in proximal coronary sinus blood, being 6 to 37 times greater than in the peripheral circulation. Comparison of the prior extraction method with direct RIA revealed a good correlation (r = 91) in samples containing higher than 100 pg/ml ANF. No correlation was observed with lower values. The elution profiles of reverse-phase HPLC of peripheral and coronary sinus plasma extracts were similar but somewhat complex, with the main immunoreactive peak corresponding to a low-molecular-weight peptide.

Adult↗
PubMed1986

Dehydration-induced changes in the secretion of atrial natriuretic factor in Brattleboro rats: effect of water-drinking.

The secretion of atrial natriuretic factor (ANF) was measured in Brattleboro rats (DI) subjected to 20-h dehydration and in normal Long-Evans rats (LE) subjected to 72-h dehydration and 7 times within the hour following voluntary rehydration by drinking water. In these rats, water deprivation caused a large, significant drop in plasma immunoreactive ANF (IR-ANF). Drinking water did not restore plasma IR-ANF values within one hour, even when indirect indices of intravascular volume such as serum osmolality, sodium and hematocrit returned to normal. The dehydration-induced decrease in plasma IR-ANF and its very low secretion after restoring drinking may be essential for the homeostasis of water conservation in both DI and LE rats.

Animals↗
PubMed1986

Increased plasma immunoreactive atrial natriuretic factor concentrations in salt sensitive Dahl rats.

We measured the immunoreactive atrial natriuretic factor concentrations in plasma and right and left atria of salt-sensitive, salt-resistant Dahl rats and Wistar Kyoto rats, all fed for 5 weeks by 8% salt diet. We found an increase in plasma immunoreactive atrial natriuretic factor (p less than 0.001) in salt-sensitive Dahl rats which became severely hypertensive in comparison with salt-resistant and Wistar Kyoto rats which remained normotensive on the same diet. There were however, no differences in the immunoreactive atrial natriuretic factor concentrations in the atria between the three groups of rats; all rats tended to have lower concentrations in the left than in the right atrium. The data show the presence of increased circulating atrial natriuretic factor immunoreactivity in hypertensive salt-sensitive Dahl rats which may be due either to the hypertension-induced left atrial distention, to volume expansion or indirectly renal hyposensitivity to the atrial natriuretic factor in these rats.

Animals↗
PubMed1986

Comparative biological activities of ANF (Arg 101-Tyr 126) and the synthetic form of circulating ANF (Ser 99-Tyr 126).

The biological activities of ANF (Arg 101-Tyr 126) and of the circulating form, ANF (Ser 99-Tyr 126), were compared in the following assays: precontracted rabbit aortic strip and chick rectum, rat natriuresis, inhibition of aldosterone secretion and receptor affinity in bovine and rat adrenal zona glomerulosa cells, and receptor affinity in rabbit aorta and rat mesenteric artery cells. The results demonstrate that both peptides share the same biological activities. It is concluded that the addition of two amino acids to the N-terminal of ANF (Arg 101-Tyr 126) does not modify its biological characteristics, validating thus previous research employing this peptide.

Adrenal Glands↗
PubMed1986

Effect of synthetic atrial natriuretic factor on arginine vasopressin release by the rat hypothalamo-neurohypophysial complex in organ culture.

The effect of synthetic rat atrial natriuretic factor (ANF, Arg 101-Tyr 126) was evaluated in an in-vitro model of rat hypothalamo-neurohypophysial complex (HNC) in organ culture in which part of hypothalamus containing a portion of undamaged magnocellular neurons is separated from posterior pituitary by a fluid tight barrier with an intact stalk connecting both structures. ANF, when added to the medium at the hypothalamus site at concentrations of 3 X 10(-5) M to 3 X 10(-7) M, did not change basal AVP release from the posterior pituitary. Similarly, a shorter form of ANF (Cys 105-Tyr 126), reported to be highly potent in inhibiting adenylate cyclase activity in various tissues, exerted no effect on AVP excretion from HNC in organ culture. The application of an hyperosomotic medium (osmolality 324 +/- 2 mOsm/kg H2O) to the hypothalamic side, together with ANF (3 X 10(-6) M), significantly lowered osmotically-stimulated AVP release. It is concluded that ANF has no effect on basal AVP release from HNC in culture and suppresses osmotically-stimulated AVP secretion in this in vitro model.

Animals↗
PubMed1986

ANF-like peptide(s) in the peripheral autonomic nervous system.

The recent demonstration of the atrial natriuretic factor (ANF) within the brain has been extended in the present study by the additional localization of ANF-like activity in the peripheral nervous structures. Using a sensitive radioimmunoassay, it was possible to detect ANF-like immunoreactive peptide(s) in crude and chromatographically separated extracts of parasympathetic rat ganglia. The partially purified ANF-like peptide exhibited a biological action similar to cardiac ANF. This finding supports a possible involvement of ANF in the regulation of both, central and peripheral neuronal activities.

Adrenal Cortex↗