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.

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.

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.

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.

Effect of natural and synthetic atrial natriuretic factor on arterial blood pressure, natriuresis and cyclic GMP excretion in spontaneously hypertensive rats.

The differential effects of extracted and synthetic atrial natriuretic factor (ANF) on arterial blood pressure, natriuresis, and cyclic GMP excretion were studied in normotensive (WKY) and spontaneously hypertensive (SHR and SHRSP) rats. Atrial extracts or synthetic (101-126)-ANF decreased arterial blood pressure in all tested animals, but the blood pressure-lowering effect was more pronounced in hypertensive than in normotensive rats. ANF-induced diuresis and natriuresis were two- to three-fold higher in the hypertensive groups.

Atrial natriuretic factor inhibits Ca(2+)-dependent K+ fluxes in cultured vascular smooth muscle cells.

The interaction of the synthetic fragment Arg101-Tyr126 of atrial natriuretic factor (ANF) with Ca(2+)-dependent K+ efflux was studied in the following six different cell models: cultured vascular smooth muscle cells from rat aorta; isolated rat glomeruli; human platelets; cultured endothelial cells from bovine aorta; peritoneal mouse macrophages; human red cells. In human red cells and mouse macrophages, the dose-response curves of K+ efflux as a function of Ca2+ ionophore, A23187, concentration were not modified by addition of ANF. In endothelial cells and platelets, ANF slightly inhibited Ca(2+)-dependent K+ efflux.

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.

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.

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.

Reduction of blood pressure and increased diuresis and natriuresis during chronic infusion of atrial natriuretic factor (ANF Arg 101-Tyr 126) in conscious one-kidney, one-clip hypertensive rats.

Conscious one-kidney, one-clip hypertensive rats and their normotensive controls were infused during 7 days with synthetic ANF (Arg 101-Tyr 126) at 100 ng/hr/rat (35 pmol/hr/rat) by means of osmotic minipumps. The basal blood pressure of 193 +/- 6 mmHg gradually declined to 145 +/- 6 mmHg at day 4 after the infusion was started. No changes in blood pressure were observed in ANF-infused normotensive rats.

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.

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.

Chronic infusion of low doses of atrial natriuretic factor (ANF Arg 101-Tyr 126) reduces blood pressure in conscious SHR without apparent changes in sodium excretion.

Conscious SHR and WKY rats were infused during 7 days with synthetic ANF (Arg 101-Tyr 126), 100 ng/hr/rat (35 pmol/hr/rat) by means of miniosmotic pumps. The SHR initial blood pressure of 177 +/- 5 mmHg gradually dropped to 133 +/- 3 and 142 +/- 4 mmHg the last two days of infusion. No significant change in blood pressure was observed in the ANF-infused WKY group.

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.

Localization of immunoreactive synthetic atrial natriuretic factor (ANF) in the heart of various animal species.

The localization of two synthetic fragments of the C-terminal portion of atrial natriuretic factor: Arg 101-Tyr 126 which displays full biological activity and Leu 94-Arg 109 which is completely devoid of biological activity, has been investigated by immunohisto- and immunocytochemical methods in the heart of mammals (rat, mouse, guinea pig, hamster, rabbit, cat, dog, man) and nonmammalian vertebrates toad (Bufo marinus), frog (Rana catesbeiana), fish (Cyprinus carpio, Puntius schwanenfeldi, Cichlosoma biocellatum, Carrasius auratus), snake (Python reticulatus) and hen. Antibodies against the synthetic fragments of ANF were raised in rabbits and used either for immunofluorescence (Coons' technique), immunohistochemistry (unlabeled antibody technique) or immunocytochemistry (protein A-gold technique). Results obtained by immunofluorescence and by the unlabeled antibody technique were similar: antibodies against Arg 101-Tyr 126 ANF allowed visualization of granulated cardiocytes in the atria of all mammals.

Vascular and adrenal receptors for atrial natriuretic factor in the rat.

Previous studies have shown that atrial natriuretic factor, a powerful vasorelaxant of precontracted vessels, inhibits the secretion of aldosterone stimulated by angiotensin II, adrenocorticotropic hormone, and potassium. We now report the presence of specific binding sites for atrial natriuretic factor in rat blood vessels (mesenteric and renal arteries) and adrenal capsules. Radioiodinated synthetic atrial natriuretic factor bound to a single class of high-affinity (KD = 0.

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.

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.

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.

Immunocytochemical localization of renin in juxtaglomerular cells.

The involvement of various organelles in the synthesis, transport, and packaging of renin in the juxtaglomerular cells of newborn mice has been investigated by immunocytochemistry with the protein A-gold technique. Highly specific rabbit antibodies against mouse submandibular renin were used. Mild fixation and embedding in glycol methacrylate allowed enough sensitivity to identify a steep gradient of labeling from rough endoplasmic reticulum to Golgi complex to secretory granules.

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.