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J Genest

Publications and source records attributed to J Genest.

At least 163 records · Page 9Linked to original sources
PubMed1986

ANF stimulation of detergent-dispersed particulate guanylate cyclase from bovine adrenal cortex.

Particulate guanylate cyclase from bovine adrenal cortex can be stimulated by ANF. A 2-fold stimulation of the enzyme was obtained with 100 nM ANF and a half-maximal stimulation, with a 5 nM dose. The stimulation by ANF persisted for at least 30 min. Various detergents, such as Triton X-100, Lubrol PX, cholate, CHAPS, digitonin and zwittergent, stimulated several-fold the activity of particulate guanylate cyclase. However, only Triton X-100 dispersed particulate guanylate cyclase without affecting its response to ANF. The dose-response curve of ANF stimulation of the particulate and the Triton X-100 dispersed enzyme was similar. The dispersion of a fully responsive guanylate cyclase to ANF will help us to uncover the type of interactions between guanylate cyclase and ANF. It will also be used as a first step for the purification of an ANF-sensitive particulate guanylate cyclase.

Adrenal Cortex↗
PubMed1986

The atrial natriuretic factor.

In less than three years since the rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats was reported the factor responsible for the diuretic, natriuretic, and vasodilating activity of the atrial homogenates was isolated, its chemical structure elucidated, and its total synthesis achieved. Also the cDNA and the gene encoding for the atrial natriuretic factor in mice, rats, and man have been cloned and the chromosomal site identified. The major effects of this hormone are vasodilatation, prevention and inhibition of the contraction induced by noradrenaline and angiotensin II, diuresis, and natriuresis associated in most instances with a pronounced increase in glomerular filtration rate and filtration fraction, inhibition of aldosterone secretion, and considerable stimulation of particulate guanylate cyclase activity. High density specific binding sites have been demonstrated in the zona glomerulosa of the adrenal cortex, in the renal glomeruli, and in the collecting ducts, and in the brain areas involved in the regulation of blood pressure and of sodium and water (AV3V region, subfornical organ, nucleus tractus solitarius, area postrema).

Adrenal Cortex↗
PubMed1986

Nutritional management of hypertension: past, present, and future.

A succinct overview of the nutritional management of hypertension, past, present, and future is presented. Prior to 1945, the low sodium diet and the rice-fruit diet were shown to be effective in reducing the blood pressure to normal levels in 35-40% of hypertensive patients. Between 1945 and the present, many studies were made on the effects of alcohol, water hardness, obesity, moderate restriction of sodium with increased potassium intake, increased dietary calcium, low animal and high unsaturated fat intake, and increased amounts of fiber in the diet. Criticisms are made of the very small magnitude, even if statistically significant, of blood pressure decreases and the too-short control periods in many instances, and also concerning the assumption of use of 24-h urinary sodium as an accurate index of the sodium intake, and of urinary creatinine as a physiological reference standard against the excretion of sodium. The author mentions, for possible future research, long-term studies of the effects of diets moderately restricted in sodium and high in potassium, of reducing weight and increasing physical activity in obese hypertensives, and of low animal and high polyunsaturated fat diets in patients with mild essential hypertension.

Blood Pressure↗
PubMed1986

Atrial natriuretic factor and vasopressin during dehydration and rehydration in rats.

To determine the effect of water deprivation (mixed volume and osmotic stimulus) on the secretion of atrial natriuretic factor (ANF) and arginine vasopressin (AVP), plasma immunoreactive ANF (IR-ANF), and plasma AVP were measured in normal conscious Sprague-Dawley rats. IR-ANF was decreased to 19.9 +/- 3.6 pg/ml (24 h dehydration), 9.8 +/- 2.5 pg/ml (48 h dehydration), and undetectable level (72 h dehydration) from the control level of 62.4 +/- 2.4 pg/ml. These decreases were accompanied by significant increase in plasma AVP, serum Na+, osmolality (osm), and hematocrit (Hct). In animals deprived of water for 3 days the secretion of ANF and AVP was monitored at seven time points during the 1st h after voluntary rehydration with tap water. After rehydration, IR-ANF was elevated dramatically within 3 min and gradually for up to 1 h after water was offered; AVP decreased within 3 min of rehydration and stayed at the water-repleted level during the next 1 h. Na+, osm, and Hct did not change until 15, 9, and 30 min after rehydration, respectively. The rapid modifications in plasma IR-ANF and AVP were accompanied by a transient but significant increase in arterial blood pressure for up to 15 min after water consumption. These results indicate that oropharyngeal-gastric stimuli contribute to the release of both ANF and AVP.

Animals↗
PubMed1986

Zona glomerulosa cell responses to atrial natriuretic factor in genetically hypertensive rats.

We examined whether abnormalities in target cell responsiveness to atrial natriuretic factor (ANF), similar to those previously found in the kidney, could also be present in the zona glomerulosa cells of spontaneously hypertensive rats (SHR) and salt-sensitive Dahl rats (S rats). We found an attenuated aldosterone (Aldo) response to angiotensin II (ANG II) in zona glomerulosa cell suspensions isolated from hypertensive SHR compared with those from Wistar-Kyoto (WKY) rats, whereas cells derived from hypertensive S rats showed a significantly higher Aldo response to the maximum stimulatory dose of ANG II than those from salt-resistant Dahl rats (R rats). The maximum observed Aldo responses to ACTH stimulation were not different in SHR or S rats compared with their respective controls. ANF exerted a potent inhibitory action on both ANG II- and ACTH-stimulated secretions of glomerulosa cell suspensions, without any difference in its potency between hypertensive and control rats. The equipotent inhibitory action of ANF on the ANG II- and ACTH-stimulated secretion of Aldo in those cell suspensions suggests that the previously observed alterations in the target cell responsiveness to ANF do not exist in the adrenal zona glomerulosa cells of SHR and Dahl S rats.

Adrenocorticotropic Hormone↗
PubMed1986

Effect of atrial natriuretic factor on adenylate cyclase in various nephron segments.

The effects of rat synthetic atrial natriuretic factor (ANF) [Arg101, Tyr126] were studied on adenylate cyclase activity in various renal structures such as glomeruli, proximal tubules, loops of Henle, and collecting ducts from dog kidney. ANF inhibited adenylate cyclase activity in glomeruli, loops of Henle, and collecting ducts, but not in proximal tubules, in a concentration-dependent manner. The maximal inhibitions observed were approximately 45% in glomeruli and collecting ducts with an apparent Ki of 10(-10)-10(-9) M and 30% in loops of Henle with an apparent Ki of 10(-11)-5 X 10(-10) M. ANF also inhibited the stimulatory responses of various hormones and forskolin on adenylate cyclase in glomeruli, collecting ducts, and loops of Henle. However, the extent of inhibition varied in the three fractions. In addition, ANF showed an additive effect with the inhibitory response of angiotensin II on adenylate cyclase in glomeruli. These data indicate that ANF receptors coupled to adenylate cyclase are present in glomeruli, loops of Henle, and collecting ducts and not in proximal tubules, and it can be suggested that the inhibition of adenylate cyclase by ANF may be one of the mechanisms through which ANF regulates kidney functions.

Adenylyl Cyclase Inhibitors↗
PubMed1986

Distinct localization of atrial natriuretic factor and angiotensin II binding sites in the glomerulus.

A comparative study of the localization of 125I-labeled atrial natriuretic factor (ANF) and 125I-labeled angiotensin II (ANG II) binding sites in the glomerulus of the rat, after an intravascular injection, has been done by ultrastructural radioautography. 125I-ANF binding sites are localized predominantly on the podocytes of the visceral epithelium (63%) followed by the endothelium of capillaries (14%), the parietal epithelium (13%), and finally mesangial cells (10%). In a comparative study, it was confirmed that 125I-ANG II uptake is localized predominantly on mesangial cells (60%) followed by epithelial visceral cells (23%) and the endothelium of capillaries (16%). Using isolated rat glomeruli, it was confirmed that ANG II decreases glomerular size (maximum effect of 15%) with an apparent half maximum effective concentration (EC50) between 10(-9) and 10(-8) M. Although ANF alone has no apparent effect on glomerular size, it inhibits the contractile effect of ANG II with a half maximum inhibitory concentration (IC50) between 10(-11) and 10(-10) M. These results suggest that an intraglomerular mechanism other than glomerular arteriolar resistance may be involved in the modulation of glomerular filtration rate by ANF. The presence of 125I-ANF uptake mainly in foot processes of visceral epithelial cells of glomeruli in vivo and the inhibition of ANG II decrease in glomerular size by ANF in vitro raise the possibility that ANF may regulate the ultrafiltration coefficient by two mechanisms: modulation of glomerular permeability, and surface area.

Angiotensin II↗
PubMed1986

Chronic estradiol treatment decreases angiotensin II receptor density in the anterior pituitary gland and adrenal cortex but not in the mesenteric artery.

Chronic estrogen treatment has been shown to produce a marked reduction in anterior pituitary angiotensin II (AII) receptor density. In order to determine whether this effect is generalized, we studied the effect of chronic estradiol treatment on AII receptor density in the anterior pituitary gland, adrenal cortex and mesenteric artery of ovariectomized (OVX) rats. Treated rats were injected daily with 25 micrograms of estradiol valerate while controls received only the vehicle. Binding affinity and density of AII receptors were measured using the AII antagonist [125I]-Sar1Ile8 AII ([125I]-SARILE). Following 7-, 14- or 28-day treatments, AII receptor density decreased by approximately 80% in the anterior pituitary; 30% in the adrenal cortex and remained the same in mesenteric artery particulate fractions. In all 3 target tissues, dissociation constants (KD) for binding of [125I]-SARILE were in the nanomolar range and were the same between control and treated rats. Using conscious rats, estradiol treatment for 7 days was also shown to block the release of aldosterone by low dose infusions of AII (10 ng/min, 30 min). Plasma AII and plasma renin activity were also the same or slightly decreased following estradiol treatments. This study suggests that estrogens may be important modulators of the AII receptor and may be directly involved in modulating target cell responsiveness to AII as expressed through differential down-regulation of AII receptors.

Adrenal Cortex↗
PubMed1986

Radioautographic localization of 125I-atrial natriuretic factor binding sites in the brain.

Rats were injected through the carotid artery (cephalad direction) with 18.9 mu Ci of either 125I-Arg 101-Tyr 126 atrial natriuretic factor alone or together with an excess of unlabeled hormone. At 2 min after injection, all rats were fixed in vivo by perfusion and serial sections of the whole brain were processed for light microscope radioautography. The radioautographic reaction produced by 125I-atrial natriuretic factor alone was localized in all circumventricular organs (except the subcommissural organ), the smooth muscle cells and endothelial cells of arteries, arterioles, veins, venules, the endothelial cells of intraparenchymal capillaries and the epithelial cells of the choroid plexus. In rats which received 125I-atrial natriuretic factor plus an excess of unlabeled hormone, the radioautographic reaction was reduced by 70-90%. Binding sites are thus localized in regions of the brain, some of them involved in the central monitoring of blood pressure and osmolarity. In addition, the presence of binding sites in the cerebral vasculature and in the epithelium of the choroid plexus suggests that circulating ANF may play a role in the control of cerebral blood flow and in the production of vertebrospinal fluid.

Animals↗
PubMed1986

Fate of [125I]angiotensin II in adrenal zona glomerulosa cells.

Binding and internalization of [125I]angiotensin II (AII) were studied by morphological and biochemical methods in rats in vivo. Light microscope radioautography demonstrated that [125I]AII binds specifically to adrenal zona glomerulosa (ZG) cells. Ultrastructural radioautographic analysis revealed that [125I]AII binds to the cell surface, clusters in coated pits, is internalized in coated vesicles, and is transported by receptosomes to lysosomes in less than 20 min. Biochemical analysis revealed that as much as 40% of the adrenal radioactive uptake behaves as native [125I]AII as shown by electrophoresis, immunoprecipitation and radioligand binding studies. These results indicate that the effects of AII on the secretion of aldosterone by ZG cells are mediated by cell surface phenomena and not by binding to intracellular organelles involved in steroidogenesis. They also indicate that the half-life of AII bound to receptors and internalized seems to be much longer (min) than in the systemic circulation (sec).

Adrenal Cortex↗
PubMed1986

Internalization and lysosomal association of [125I]angiotensin II in norepinephrine-containing cells of the rat adrenal medulla.

The morphological localization of [125I]angiotensin II (AII) in the rat adrenal medulla (AM) was studied by light- and electron-microscopic radioautography in vivo. With light microscopy the presence of binding sites for AII in both norepinephrine-containing (NE) and epinephrine-containing (E) cells was confirmed. With electron microscopy, it was found that AII binds to the cell surface of NE cells, is progressively internalized, and is associated with lysosomes and Golgi complex within 20 min, whereas in E cells AII seems to be internalized earlier and recycled back to the cell surface within 5 min without any appreciable association with intracellular organelles. These results suggest different intracellular pathways for AII in NE and E cells of the rat AM.

Adrenal Medulla↗
PubMed1986

Localization and characterization of specific receptors for atrial natriuretic factor in the ciliary processes of the eye.

By light and electron microscope radioautography in vivo, competitive binding sites for 125I-Arg 101-Tyr 126 atrial natriuretic factor were localized mostly on the "pigmented" epithelium of the rat ciliary process. Further investigation using isolated ciliary processes from rabbits demonstrated the presence of specific receptors for 125I-atrial natriuretic factor. In addition, synthetic atrial natriuretic factor inhibited basal and stimulated adenylate cyclase activity. These results demonstrate for the first time the presence of specific receptors for atrial natriuretic factor in the ciliary processes which are negatively coupled to adenylate cyclase. The possible role of this peptide in the control of intraocular pressure is suggested.

Adenylyl Cyclases↗
PubMed1986

Involvement of the adrenal glands in the action of the atrial natriuretic factor.

Adrenalectomized, medullectomized and sham operated rats were treated with either a chronic infusion or a bolus injection of the synthetic atrial natriuretic factor (ANF). ANF did not enhance natriuresis and diuresis in sham operated conscious animals during chronic infusion, but it had a potent action when injected as a bolus into anesthetized rats. The absence of the whole adrenal glands, but not adrenal medulla profoundly modified the renal response to ANF: a) following chronic administration of ANF, the baseline natriuresis paradoxically decreased in adrenalectomized rats, and b) in response to a bolus injection of ANF the natriuretic and diuretic actions of the peptide were attenuated in these animals. The medullectomy-induced decreased natriuresis and dopamine excretion were corrected by ANF infusion. Furthermore, ANF suppressed the compensatory increase of norepinephrine excretion secondary to adrenalectomy. The data suggest that the presence of the adrenal cortex is necessary for the natriuretic and diuretic actions of ANF. The decrease in urinary DA excretion may reflect diminished dopaminergic activity and contribute to the post-medullectomy antinatriuresis, a phenomenon which can be corrected by ANF infusion. ANF may also have a depressing activity on the increased sympathetic tone.

Adrenal Glands↗
PubMed1986

Atrial natriuretic factor inhibits the sympathetic nervous activity in one-kidney, one-clip hypertension in the rat.

The one-kidney, one-clip model of rat hypertension was found to have an increased natriuresis following chronic infusion of atrial natriuretic factor (ANF). We have now found that this natriuretic effect of ANF is associated with a suppression of the initially elevated urinary excretion of norepinephrine and epinephrine and increase of the excretion of the main dopamine metabolite-dihydroxyphenylacetic acid as well as of the urinary dopamine to norepinephrine ratio. These data are compatible with the hypothesis that ANF suppresses the increased sympathetic activity in this model of hypertension and this action combined with opposite changes of dopamine may contribute to the natriuretic effect of ANF.

Animals↗
PubMed1986

Identification of the released form of atrial natriuretic factor by the perfused rat heart.

Atrial natriuretic factor (ANF), released by the isolated perfused rat heart, was extracted from the perfusates by C18 Sep-Pak cartridges and then isolated by immunoaffinity chromatography and by reverse phase HPLC. About 500 ng of immunoreactive material were so obtained and submitted to amino acid sequencing. The C-terminal Tyr was detected by radiolabelling. Identification of these residues indicated that the primary structure corresponds to ANF (Ser 99-Tyr 126) which is identical to the circulating form in the rat. These results indicate that the ANF released by the atria corresponds to a short peptide. Therefore, its maturation process may therefore take place either intracellularly or during secretion and implicates a tryptic-like cleavage after a single Arg residue in position 98.

Amino Acid Sequence↗
PubMed1986

The blood pressure decrease-induced sympathetic discharge following atrial natriuretic factor administration may offset its natriuretic action.

Conscious SHR and WKY rats were infused during 7 days with ANF (Arg 101-Tyr 126), 100 ng/hr/rat, by means of miniosmotic pumps and their basal blood pressure (BP), changes in sodium excretion and urinary catecholamines compared with those at the last day of the infusion. The SHR initial BP of 181 +/- 3 mmHg gradually declined to 137 +/- 5 mmHg. No significant change in blood pressure was observed in the ANF-infused WKY group. However, WKY rats exhibited an increased sodium excretion and urinary dopamine/norepinephrine ratio when compared to sham-infused rats. No such differences were observed in SHR. It is suggested that an ANF-induced withdrawal of the renal sympathetic tone permits the manifestation of its natriuretic action in WKY rats. When, however, a BP decrease predominates, as in SHR, this decrease results in a reflex sympathetic discharge with a renal sympathetic activity over-riding the ANF induced natriuresis seen in WKY rats. Secondary sympathetic responses to the ANF-induced BP decrease have to be thus taken into account when a dissociation between the hypotensive and natriuretic action of ANF is observed in vivo.

Animals↗