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Biomedical subjects

J Genest

Publications and source records attributed to J Genest.

At least 181 records · Page 10Linked to original sources
PubMed1986

Cyclic GMP as mediator and biological marker of atrial natriuretic factor.

Both our previous and the present studies established that increases in cyclic guanosine monophosphate (cGMP) reflect the activity of atrial natriuretic factor (ANF). The ANF message is transmitted by particulate guanylate cyclase, which appears to be in intimate contact with the ANF receptor since stimulation of particulate guanylate cyclase is observed even after dispersion of the membranes. The stimulation of smooth muscle and endothelial cells in culture leads to egression of cGMP to extracellular medium where it accumulates for over 2 h. The signal of the extracellular cGMP is magnified and prolonged compared to the intracellular signal. The stimulation of cGMP production by ANF in vascular smooth muscle and endothelial cells appears to be relatively irreversible and the responsiveness is down-regulated by prior exposure to low doses of ANF. Cyclic guanosine monophosphate can also serve as a marker for ANF action. Atrial natriuretic factor fragments of different potencies exert a biological activity that correlates with ANF-induced cGMP increases. In hypertensive rats and monkeys, where acute infusion of ANF leads to an exaggerated diuresis and natriuresis, urinary cGMP does not appear to be different. Overall, cGMP appears to be a mediator and a marker of ANF biological activity and may serve as a useful tool in the study of pathogenesis of hypertension.

Animals↗
PubMed1986

Some physiopathological aspects of atrial natriuretic factor.

Chronic infusion of atrial natriuretic factor (ANF) decreased blood pressure in two-kidney, one clip (2-K, 1C), spontaneously hypertensive rat (SHR) and one-kidney, one clip (1-K, 1C) models of experimental hypertension in the rat, but produced increased sodium excretion only in the 1-K, 1C model. In ANF-infused 2-K, 1C animals plasma renin activity did not differ from normotensive controls. Atrial content of immunoreactive (ir) ANF was significantly lower in SHR and 1-K, 1C animals. At 40-50 days old, cardiomyopathic hamsters had a higher concentration of plasma irANF and a lower ANF content in the left but not in the right atrium, although the difference in plasma ANF was more obvious once heart failure was well established. At 110-130 and 200-300 days old, the hamster atrial ANF content was not only lower in the left but also in the right atrium. No differences were observed in plasma irANF between normal subjects and either untreated or treated essential hypertensive patients. However, a significantly higher plasma ANF was observed in two groups with secondary hypertension, primary hyperaldosteronism and renovascular hypertension. Bolus injection of ANF into healthy subjects produced a dose-related decrease in blood pressure and an increase in the heart rate and natriuresis.

Adult↗
PubMed1986

Effect of dietary sodium on plasma concentration of immunoreactive atrial natriuretic factor in normal humans.

Atrial natriuretic factor (ANF) is the name applied to a family of peptides secreted by the atria, endowed with potent natriuretic, vasorelaxant, and aldosterone inhibitory properties, and which has been purified from animal and human atria. A radioimmunoassay of human plasma ANF was developed. Six normal men, aged between 24 and 38, were studied after 4 days on a low-sodium diet (40 mmol per day) and 4 days on a high-sodium diet (300 mmol per day), in random order. Plasma renin activity was suppressed and plasma aldosterone reduced by the high-sodium diet, as expected. Plasma immunoreactive ANF was 47.9 +/- 4.8 pg/ml on the low-sodium diet and rose to 68.1 +/- 5.9 pg/ml on the high-sodium diet (p less than 0.01). These results demonstrate that secretion of ANF by the heart may be modulated by the changes produced by extreme variations in sodium intake.

Adult↗
PubMed1986

The heart as an endocrine gland.

Two independent series of biomedical investigations have led to the discovery that the atria constitute a peptide-secreting endocrine gland. The first investigation is mainly morphological and started with the finding that mammalian atrial (but not ventricular) cardiocytes contain "dense bodies." These "dense bodies," later called "specific granules," were found to be different from lysosomes; to be made up of proteins; and to incorporate both 3H-leucine and 3H-fucose in a pattern typical of peptide-secreting endocrine cells. The finding that rat atrial granulation varied with the sodium and water balance led to the crucial observation that atrial extracts have natriuretic and diuretic effects. In less than five years, this new natriuretic hormone has been purified, sequenced and synthesized, and its CDNA and gene have been cloned. The atrial natriuretic factor (ANF) gene has been assigned to the distal short arm of chromosome 1 in band 1P36, while the mouse gene is localized in chromosome 4. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are already beginning to emerge. Concurrently, the search for the function of natriuretic hormones or factors (through studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibition, and parabiosis experiments in Dahl rats) has provided a general framework within which to interpret this new cardiac function.

Animals↗
PubMed1986

Episodic dopamine discharge in paroxysmal hypertension. Page's syndrome revisited.

Dopamine concentration, a marker of the sympathetic discharge additional to norepinephrine and epinephrine levels, was determined in 31 patients. These patients, mostly women, had essential hypertension and hypertensive episodes that mimicked pheochromocytoma, except that the patients were rather plethoric (instead of pale) and often had associated nausea, epigastric discomfort, and polyuria. During and after hypertensive paroxysms, plasma free norepinephrine and epinephrine levels did not increase, but we found a mean eightfold and 16-fold increase of free and sulfated plasma dopamine levels, respectively, and similar although less marked dopamine level increases in the urine collected following the paroxysm. The hypertensive paroxysms, spontaneous or precipitated by stimulation of the autonomic nervous system, were similar to those described by Page as simulating diencephalic stimulation. Dopamine level may be a marker of the sympathetic discharge, undetected by measurements of free norepinephrine level, and may explain some clinical features of Page's syndrome.

Adrenal Gland Neoplasms↗
PubMed1985

Partial characterization and solubilization of receptors for atrial natriuretic factor in rat glomeruli.

Specific receptors for atrial natriuretic factor (ANF) have been identified and solubilized in glomeruli from rat kidney. Radioiodinated synthetic ANF (Arg 101-Tyr 126) bound to a single class of high affinity (Kd 27 +/- 24 pM) sites with a density of 390 +/- 230 fmole/mg protein. The binding was time- and temperature-dependent, saturable and reversible. The ANF-receptor complex was not affected by angiotensin II, ACTH or vasopressin. Solubilization with 10 mM 3-[(3-cholamidopropyl)-dimethylammonio]- 1-propane sulfonate (CHAPS) slightly increased the affinity for ANF (Kd 5.0 +/- 3.3 pM) without affecting the density (250 +/- 110 fmole/mg protein). Similar results were found with 1% Triton X-100. ANF-related peptides interact generally in the same way with non-solubilized and solubilized receptors, indicating a fully preserved specificity of the receptors.

Adrenocorticotropic Hormone↗
PubMed1985

Structure-activity relationships of atrial natriuretic factor (ANF). III. Correlation of receptor affinity with relative potency on aldosterone production in zona glomerulosa cells.

The activity of various fragments of ANF as inhibitors of aldosterone secretion and as competitors of [125I] ANF (Arg101-Tyr126) binding to specific receptors was studied in bovine zona glomerulosa. Shortening or lengthening the N-terminal segment of ANF does not alter its biological activity while minimally altering affinity for its receptor. Removal of the C-terminal to Cys121 or expansion up to Arg128 leads to 1000-fold decrease in receptor affinity and activity. The results indicate the importance of the C-terminal segment of ANF in determining its active conformation.

Adrenal Cortex↗
PubMed1985

Gluco- and mineralocorticoids may regulate the natriuretic effect and the synthesis and release of atrial natriuretic factor by the rat atria in vivo.

Adrenalectomy abolished the acute natriuretic effect of ANF which was partially restored to about 50% by combined therapy with gluco- and mineralocorticoids. It is suggested that the lack of effect of ANF may be due to a decreased renal vascular reactivity to the peptide in adrenalectomized animals. Simultaneous administration of Dexamethasone and Deoxycorticosterone acetate to adrenalectomized rats produced a marked increase in immunoreactive ANF in atrial tissue and plasma. The administration of NaCl to these animals produced a relatively lower concentration of atrial ANF and a further increase in plasma ANF. Our results suggest that glucocorticoids may regulate synthesis and release of ANF by the atria and mineralocorticoids may have a permissive role. Furthermore, the presence of steroids is necessary for the NaCl-stimulated ANF release.

Adrenalectomy↗
PubMed1985

Identification of a biologically active circulating form of rat atrial natriuretic factor.

An atrial natriuretic peptide has been isolated from plasma of morphine treated rats by means of glass beads extraction, immunoaffinity chromatography, and reverse phase HPLC. 1.3 micrograms of immunoreactive material was obtained. The biological activity of this material was found comparable to that of ANF (Arg 101 - Tyr 126) on the inhibition of basal aldosterone secretion by rat adrenal zona glomerulosa cells and the displacement curve of iodinated ANF from ANF receptors in a mesenteric artery preparation. Gas phase amino acid sequencing indicated that it is related to ANF (Ser 99 - Tyr 126). These results suggest that the maturation of ANF may require a tryptic-like cleavage after a single Arg residue.

Adrenal Cortex↗
PubMed1985

ANF (Arg 101--Tyr 126) is the peptide secreted by rat atrial cardiocytes in culture.

The atrial natriuretic factor (ANF) secreted from rat cardiocytes in culture was purified and characterized. The purification procedure involves extraction of ANF by activated Vycor glass, followed by HPLC on C18 mu Bondapak and Vydac columns. The detection of ANF in column eluates was performed by a simple and sensitive radioimmunoassay. The amino acid composition and N-terminal amino acid sequencing appeared to be identical to the Arg 101 - Tyr 126 peptide. The isolated ANF showed biological activity, inhibiting basal and ACTH-stimulating aldosterone secretion from rat zona glomerulosa cells with the same potency as the synthetic peptide.

Adrenal Glands↗
PubMed1985

Effect of different anesthetics on immunoreactive atrial natriuretic factor concentrations in rat plasma.

The effect of different conditions of blood withdrawal and use of different anesthetics on immunoreactive atrial natriuretic factor (IR-ANF) concentrations in plasma was studied in rats. The concentration of IR-ANF in plasma from jugular vein of non-anesthetized conscious rats, cannulated either 24 hr before blood withdrawal was 93.9 +/- 17.1 pg/ml (n = 30); and 48 hr: 81.9 +/- 11.5 pg/ml (n = 29). Immobilization stress (4 hr) increased IR-ANF concentration: 248.0 +/- 80.2 pg/ml (n = 5). Anesthesia by morphine, diethyl-ether, chloral hydrate and ketamine chlorhydrate increased IR-ANF concentrations to 2,443.0 +/- 281.2 pg/ml (n = 24), 806.1 +/- 74.6 pg/ml (n = 64), 224.0 +/- 81.4 pg/ml (n = 20), and 195.0 +/- 20.3 pg/ml (n = 51), respectively. IR-ANF in plasma of sodium-pentobarbital and urethane anesthetized rats was 59.2 +/- 6.7 pg/ml (n = 10) and 42.6 +/- 8.1 pg/ml (n = 8), respectively. These changes in IR-ANF evoked by different types of anesthetics and different conditions of blood withdrawal have to be taken into consideration during studies on the physiopathological role of atrial natriuretic factor.

Anesthetics↗
PubMed1985

Immunoreactive atrial natriuretic factor (IR-ANF) in human plasma.

A direct radioimmunoassay for ANF in human plasma was developed. A synthetic alpha-human atrial peptide (Ser 99-Tyr 126) was used for preparation of the iodinated tracer and the standards. The sensitivity of the method is 1.9 pg/ml. Concentration of immunoreactive ANF (IR-ANF) in plasma of 59 clinically normal subjects was 65.3 +/- 2.5 pg/ml (mean +/- SE). In two patients who underwent atrial pacing an increase of about 100 percent in circulating IR-ANF was observed. IR-ANF was extracted from human plasma by Vycor glass and purified by HPLC. The main immunoreactive isolated peak contained a low molecular weight peptide.

Atrial Natriuretic Factor↗
PubMed1985

Inhibition of pituitary adenylate cyclase by atrial natriuretic factor.

The effect of synthetic rat atrial natriuretic factor (ANF) on adenylate cyclase activity was studied in rat anterior and posterior pituitary homogenates. ANF (Arg 101-Tyr 126) inhibited adenylate cyclase activity in anterior and posterior pituitary homogenates in a concentration dependent manner. The maximum inhibitions observed were 42% in anterior pituitary with an apparent Ki of 10(-10) M, and 25% with an apparent Ki of 10(-11) M in posterior pituitary. Corticotropin-releasing factor (CRF), vasoactive intestinal peptide (VIP) and prostaglandins (PGE1) stimulated adenylate cyclase to various degrees in anterior pituitary homogenates and ANF inhibited the stimulatory effect of all these hormones. In addition ANF was also able to inhibit the stimulation exerted by NaF and forskolin which activate adenylate cyclase by receptor independent mechanism. Similarly, the stimulatory effects of N-Ethylcarboxamide adenosine (NECA), NaF and forskolin on adenylate cyclase in posterior pituitary homogenates were also inhibited by ANF. This is the first study demonstrating the inhibitory effect of ANF on pituitary adenylate cyclase.

Adenosine↗
PubMed1985

Changes of regional blood flow induced by atrial natriuretic factor (ANF) in conscious rats.

The effect of synthetic atrial natriuretic factor (ANF 101-126) has been studied on regional blood flow distribution. Microspheres (15 +/- 3 microns), labelled with either 113Sn or 57Co, were injected through an intraventricular cannula into conscious rats while a reference blood sample was withdrawn. Two minutes after the first microspheres injection either ANF or NaCl were injected. Five minutes later, the second microspheres injection was administered, and after two minutes the animals were sacrificed, and several tissues removed and counted. Percent of flow distribution, cardiac output and tissue blood flow were calculated by standard formulas. ANF produced a significant increase in absolute blood flow in lungs, heart, spleen, kidneys and testes. Total renal blood flow and total splanchnic blood flow were also increased in ANF-injected animals. No significant changes were observed in cardiac output. It is suggested that the natriuretic and hypotensive responses to ANF in vivo may be, at least partially, explained by its hemodynamic effects.

Animals↗
PubMed1985

Inhibitory effect of atrial natriuretic factor on adenylate cyclase activity in adrenal cortical membranes.

The effect of rat synthetic atrial natriuretic factor (ANF) on adenylate cyclase activity was studied in adrenal cortical membranes. Synthetic ANF (Arg 101-Tyr 126) inhibited adenylate cyclase activity in a concentration-dependent manner. The maximum inhibition observed was about 25% with an apparent ki of 5 X 10(-11) to 10(-10) M. Various hormones such as isoproterenol, dopamine, prostaglandin (PGE1) and ACTH-stimulated adenylate cyclase to various degrees and ANF inhibited the stimulatory effect of all these hormones to some degree but never abolished it. In addition, ANF was also able to inhibit the stimulation exerted by forskolin which activates adenylate cyclase by receptor-independent mechanism. This is the first study demonstrating the inhibitory effect of ANF on adrenal cortical adenylate cyclase. From these results it can be suggested that the inhibition of adenylate cyclase may be one of the mechanisms through which ANF exerts the inhibitory effect on steroidogenesis stimulated by various hormones and agents.

Adenylyl Cyclase Inhibitors↗