[Orthostatic hypotension: new therapeutic approaches].
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Atrial Natriuretic Factor↗
Biomedical subjects
O Kuchel
Publications and source records attributed to O Kuchel.
Atrial natriuretic factor in sympathetic ganglia of the rat: dependence on cholinergic innervation.
Atrial natriuretic factor is detectable in the peripheral autonomic ganglia of the rat by radioimmunoassay and immunohistochemistry. In the present study, surgical and neurochemical methods were used to evaluate the source of this peptide in sympathetic ganglia. Decentralization of the ganglia and/or central administration of colchicine diminished the atrial natriuretic factor content in para- and prevertebral ganglia. Axotomy did not affect levels of ganglionic atrial natriuretic factor. A messenger ribonucleic acid species hybridizing with rat atrial natriuretic factor complementary deoxyribonucleic acid was not found within the total ribonucleic acid extracted from superior cervical ganglia. These results indicate a direct dependence of ganglionic atrial natriuretic factor on cholinergic innervation.
Acetylcholine↗
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↗
Effects and pharmacokinetics of bolus injections of atrial natriuretic factor in normal volunteers.
The aim of this study was to examine the hemodynamic, renal, and endocrine effects of exogenous human atrial natriuretic factor (ANF), together with its pharmacokinetics, in healthy volunteers. Ten subjects participated in this study, in which the effects of a single bolus dose of ANF and of a matched vehicle injection were compared under a 135 mmol/day sodium intake. Doses of 3, 12.5, and 25 micrograms of ANF were given to 1 subject each, and doses of 50 and 100 micrograms were given to 4 and 3 subjects, respectively. Significantly, hemodynamic changes occurred at the 100 micrograms dose, when mean blood pressure decreased by 15% and heart rate increased reciprocally. Diuresis and natriuresis tended to increase following 50 micrograms but increased significantly and in a prolonged fashion following 100 micrograms of ANF. Atrial natriuretic factor did not cause significant changes in plasma catecholamine, renin activity, and aldosterone levels at any dose, although aldosterone tended to decrease. Plasma arginine-vasopressin concentrations decreased significantly following 100 micrograms. Plasma cyclic GMP levels increased in all subjects and in a dose-dependent fashion. Plasma ANF concentrations peaked 3-5 min following the bolus injection and returned toward baseline values within 10-60 min. Although with doses of less than or equal to 50 micrograms plasma ANF levels increased up to 8 to 50-fold, compared to baseline values, the only significant change was the increase in plasma cyclic GMP levels, perhaps because the effects of ANF were successfully masked by counter-regulatory mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Ganglionic immunoreactive atrial natriuretic factor in rat experimental hypertension.
Because previous data have suggested a dependence of ganglionic atrial natriuretic factor (ANF) content on preganglionic cholinergic input, we investigated the possibility that the increased neural activity observed in spontaneously hypertensive rats (SHR) may be reflected by ganglionic immunoreactive ANF levels. Four-week-old normotensive SHR had celiac ganglionic immunoreactive ANF values comparable to those of Wistar-Kyoto rats (WKY). When they became hypertensive, however, at 12 weeks of age, the SHR manifested higher immunoreactive ANF levels in celiac ganglia than the WKY group (25.3 +/- 2.6 vs 14.5 +/- 1.7 pg/ganglion; p less than 0.01), but there were no differences in levels in the superior cervical and nodose ganglia. The values in celiac ganglia were quadrupled on the average in hypertensive Dahl salt-sensitive rats under the influence of an 8% salt intake for 5 weeks, but no difference was noted in any of these ganglia between this group and their salt-resistant partners. The celiac and superior cervical ganglionic immunoreactive ANF content in normotensive Sprague-Dawley rats was higher with high salt than with normal salt intake. Hypertensive rats treated with deoxycorticosterone acetate (DOCA)-salt and sham-treated controls showed immunoreactive ANF concentrations in celiac ganglia similar to those detected in Dahl rats but, again, no differences were found between groups. Thus, hypertensive SHR, compared to WKY, have higher celiac ganglionic immunoreactive ANF levels, unlike Dahl salt-sensitive and DOCA-salt animals relative to their respective controls. This increase is unique to SHR (although all three models have elevated plasma immunoreactive ANF when they are hypertensive) and to the celiac ganglia.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
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↗
Catecholamine, dopamine-beta-hydroxylase and atrial natriuretic factor content in separate heart chambers of cardiomyopathic hamsters.
Since previous investigations have suggested a relationship between atrial natriuretic factor (ANF) and dopamine-beta-hydroxylation, cardiomyopathic hamsters were studied for atrial and ventricular catecholamine (CA) and dopamine-beta-hydroxylase (D beta H) content as correlates to a parallel finding of markedly decreased atrial but increased ventricular ANF concentrations in these animals. It was noted that, with progressive cardiomyopathy, the reduced tissue norepinephrine (NE) content paralleled the declining D beta H activity in the atria. In the ventricles, however, the progressively-decreasing NE content was associated with an increase of D beta H. These data indicate that the NE depletion is mediated by different mechanisms in the ventricles and atria. They do not support a simple relationship between NE depletion and tissue D beta H activity or between the latter and tissue ANF concentrations.
Animals↗
Atrial natriuretic factor partially inhibits the stimulated catecholamine synthesis in superior cervical ganglia of the rat.
We examined whether the atrial natriuretic factor (ANF) may affect the function of the peripheral autonomic neurons. ANF was found to inhibit the carbachol-stimulated synthesis of catecholamines from their labelled [3H]tyrosine precursor in an organ suspension of the rat superior cervical ganglia in vitro. This is compatible with the possibility that the previously observed inhibitory action of ANF on sympathetic nervous activity and the presence of immunoreactive ANF in the rat peripheral autonomic ganglia is related to an inhibitory-neuromodulatory role of ANF in the process of ganglionic neurotransmission.
3,4-Dihydroxyphenylacetic Acid↗
Plasma atrial natriuretic factor concentrations in essential and renovascular hypertension.
Plasma atrial natriuretic factor concentrations were measured in 44 patients with mild untreated essential hypertension and 48 normotensive controls. Mean venous plasma atrial natriuretic factor concentrations were 13.2 (SEM 1.5) and 13.0 (1.3) ng/l in the hypertensive patients and controls, respectively. Plasma atrial natriuretic factor concentrations were significantly correlated with age in both groups. Plasma atrial natriuretic factor concentrations were also measured during renal vein catheterisation in a group of 15 hypertensive patients; of these, eight had renovascular hypertension, and in all eight cases plasma atrial natriuretic factor concentrations were increased in the aorta and inferior vena cava. It is concluded that mild essential hypertension is not associated with increased plasma atrial natriuretic factor concentrations, whereas an age related increase in concentrations occurs in hypertensive and normotensive people.
Adult↗
An emerging relationship between peripheral sympathetic nervous activity and atrial natriuretic factor.
The sympathetic nervous system and atrial natriuretic factor (ANF) are intimately involved in sodium, volume and blood pressure homeostasis, particularly in response to volume and pressure overloads. Although rapid progress in this field indicates several levels of interaction between both systems, the role of sympathetic nervous activity (SNA) in ANF release remains a controversial topic. There is growing evidence that ANF is an inhibitory modulator of sympathetic outflow (which in turn, may contribute to ANF's effect) and, vice-versa, SNA attenuates the target actions of ANF. Compensatory sympathetic reactions to changes induced by ANF may also have an overriding influence on its target actions. Dopamine appears to play a special role in these interactions. It is not only a precursor of norepinephrine but probably fulfills an independent function in the regulation of salt balance, similar in many respects to that of ANF.
Animals↗
Modification of dopamine and norepinephrine metabolism in the rat brain by monoamine oxidase inhibitors.
The treatment of Sprague-Dawley rats with monoamine oxidase (MAO) inhibitors (pargyline, tranylcypromine) profoundly affects dopamine (DA) and norepinephrine (NE) metabolism in the brain. In these rats injection of L-dopa led to large increases in norepinephrine (NE), normetanephrine (NMN) and 3-methoxytyramine (3-MT) in brain tissues. The response of MAO-inhibited rats to L-dopa contrasted sharply with those not treated with the MAO inhibitor; the latter showed no change in NE, NMN and 3-MT after similar administration of L-dopa. The increase of NE in pargyline-treated rats correlated closely with that of DA in the hypothalamus and in the brain stem. This response was greatly diminished in rats previously treated with the neurotoxin 6-hydroxydopamine, but was restored when the treatment with 6-hydroxydopamine was accompanied by desimipramine. This suggests that noradrenergic neurons were the origin of the NE response. The NMN and 3-MT increases occurring only in the rats treated with a MAO inhibitor were highly correlated. The results suggested that MAO inhibitor may affect entry of DA into catecholaminergic storage where NE synthesis takes place and from where DA is released.
Animals↗
Responses of plasma immunoreactive atrial natriuretic factor, aldosterone and urinary dopamine to salt-loading in a patient with severe idiopathic edema.
A patient with severe idiopathic edema and long history of diuretic abuse had, in response to salt loading, an inability to increase urinary sodium excretion associated with a paradoxical response (decrease) of urinary dopamine excretion, a non suppressible aldosterone and non stimulable immunoreactive atrial natriuretic factor in plasma. These patterns distinguished this patient from those with a milder form of idiopathic edema who did not abuse diuretics and had, in comparison with controls, marginally decreased urinary sodium and dopamine responses but normal aldosterone suppressibility and ANF stimulability. Since the natriuretic action of ANF appears to be mediated by dopaminergic mechanisms, this severe natriuretic handicap may be due to a chronic diuretic abuse-induced combined ANF and dopamine deficiency.
Adult↗
Posture- and emotion-induced severe hypertensive paroxysms with baroreceptor dysfunction.
In a patient followed up for 30 years, severe but brief posture- or emotion-induced hypertensive paroxysms with flushing were associated with an increased cardiac output [inconsistently accompanied by increased plasma catecholamines (CA)] and a decreased blood pressure reactivity to norepinephrine with decreased reflex bradycardia. Sodium depletion further accentuated the latter abnormality and reproducibly reversed orthostatic hypertension to orthostatic hypotension. Abnormal responses in the Valsalva manoeuvre in an upright position suggested a defect in baroreceptor sensitivity, but may also have been due to an impaired venous return. The indices of the efferent portion of the reflex and central nervous system responses to stimuli were normal or exaggerated. The abnormality was probably due to a hypothalamic dysfunction and/or an abnormal central baroreceptor integration in the nucleus tractus solitarii. The absence of left ventricular hypertrophy and other target lesions, despite spectacular rises in blood pressure, suggests an excellent cardiovascular tolerance of hypertensive episodes if they are short-lived.
Affective Symptoms↗
Catecholamines and atrial natriuretic factor in Dahl and spontaneously hypertensive rats.
We have previously demonstrated two different catecholaminergic patterns in genetic and experimental hypertension: a hyperdopaminergic state in spontaneously hypertensive (Okamoto) rats (SHR) and a hypernoradrenergic state in salt-sensitive Dahl rats. Plasma immunoreactive atrial natriuretic factor (IR ANF) concentrations increase in both models as a response to hypertension. To distinguish between the genetic and acquired components of these abnormalities, we measured adrenal dopamine-beta-hydroxylase (D beta H) activity and coeliac ganglionic atrial natriuretic factor (ANF) like immunoreactivity in the two animal strains. While adrenal D beta H activity was increased in Dahl S rats, it was diminished in SHR in the prehypertensive as well as in the hypertensive stages. In the hypertensive stage, the ANF-like immunoreactivity in the coeliac ganglia was lower in the Dahl S group but higher in SHR than in their respective normotensive controls; there were no changes in these animals when they were prehypertensive. Differences in D beta H activity, which determines the fine tuning of sympathoadrenomedullary catecholamine synthesis may account for the inheritance of mechanisms resulting in salt-sensitive hypertension (as in SHR) or salt-dependent hypertension (as in Dahl salt-sensitive rats). In contrast, plasma IR ANF concentrations may reflect a defense mechanism against hypertension. However ANF-like immunoreactivity in coeliac ganglia does not follow its plasma concentrations and changes in different directions in the two hypertensive strains; it may reflect a neuromodulatory function of ANF in the ganglionic neurotransmission and different implications of this role of ANF in the two hypertensive models.
Animals↗
L-dopa metabolism in genetically hypertensive mice: effect of pargyline.
This study on the role of the sympathetic nervous system in the development of hypertension involves the measurement of dopamine and norepinephrine accumulation in various tissues of the hypertensive and random-bred normotensive strains of mice at basal levels, and following a pargyline-L-dopa treatment. Under such a treatment, designed to suppress the homeostatic action of monoamine oxidase and to better expose the relationship between dopamine and norepinephrine, the brain and heart of the hypertensive mice accumulated more dopamine than the normotensive mice. There was a significantly lower norepinephrine accumulation in the heart of the hypertensive mice in spite of comparable dopamine-beta-hydroxylase activity in this tissue between the two strains of mice. Under the pargyline-L-dopa treatment, the brain and heart of the older mice in both hypertensive and normotensive strains accumulated significantly (p less than 0.05) more dopamine than those of their younger counterparts, while their norepinephrine accumulation remained unchanged. The results demonstrated different patterns of response of dopamine and norepinephrine in the development of hypertension.
3,4-Dihydroxyphenylacetic Acid↗
Presence of an atrial natriuretic factor-like peptide in the rat superior cervical ganglia.
The presence of a peptide resembling atrial natriuretic factor (ANF) was demonstrated in the peripheral sympathetic ganglia of the rat by a sensitive radioimmunoassay. Partially purified ANF-like compounds from the superior cervical ganglia exhibited biological activities which were similar to the synthetic peptide of cardiac origin; they inhibited ACTH-stimulated aldosterone release in vitro and displaced labelled [125I]-ANF from rat adrenocortical cell receptors. The exact source and role of ANF in peripheral nervous structures is not fully understood. We suggest that in sympathetic ganglia ANF may act as a neurotransmitter and/or neuromodulator in a manner similar to other neuropeptides.
Adrenal Cortex↗
Abnormal adrenal catecholamine synthesis in salt-sensitive Dahl rats.
The possible role of catecholamines in the abnormal renal response to salt loading, a genetic defect resulting in hypertension in the salt-sensitive strain of Dahl rats, was investigated by measuring the adrenal synthesis of norepinephrine, epinephrine, and dopamine as well as their content in several tissues and the urinary excretion of these catecholamines as well as some of their metabolites at the height of salt-induced hypertension. We found that salt-sensitive Dahl rats, compared with salt-resistant Dahl rats, have a higher adrenal synthesis of [3H]norepinephrine following a pulse injection of [3H]tyrosine, a higher adrenal norepinephrine and epinephrine content but a lower kidney and heart ventricle content of dopamine and norepinephrine, and a decreased excretion of urinary dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, and homovanillic acid. These data suggest that the primary abnormality in salt-sensitive Dahl rats may be their inability to turn off, during high salt intake, their increased adrenal norepinephrine synthesis from dopamine. The abnormal catecholamine response of salt-sensitive Dahl rats to high salt intake indirectly suggests increased noradrenergic activity and decreased dopaminergic activity in the kidney, which may be important mechanisms in the sodium retention and hypertension of these rats.
Adrenal Glands↗
Cyclical edema and hypokalemia due to occult episodic hypercorticism.
Yearly episodes of edema, hypokalemia, anxiety, and depression were found to be due to cortisol and deoxycorticosterone surges secondary to a pituitary adenoma in a woman without any of the usual clinical features of Cushing's syndrome. During the long clinical remissions, she had no recognizable laboratory abnormality. She had two episodes in the year following incomplete transphenoidal pituitary tumor resection, but has had none in 2 yr since receiving radiotherapy. The episodes were caused by mineralocorticoid actions of large ACTH-induced increases in cortisol and deoxycorticosterone secretion. A history of episodic edema and hypokalemia, often attributed in women to surreptitious diuretic abuse, requires a careful search for hypercorticism even in the absence of clinical Cushing's syndrome.
Adenoma↗