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Biomedical subjects

K Racz

Publications and source records attributed to K Racz.

At least 19 recordsLinked to original sources
PubMed1992

Coexpression of renin, angiotensinogen, and their messenger ribonucleic acids in adrenal tissues.

The presence of the two components of the renin-angiotensin system (RAS) has been systematically investigated in human normal and pathological adrenal tissues with two aims: 1) the detection of renin and especially angiotensinogen, which has not been reported before; and 2) to study possible differences in the coexpression of renin and angiotensinogen in tissue of cortical and medullary origin. The relative levels of renin and angiotensinogen mRNAs were determined by Northern blot analysis in normal (n = 5) and pathological adrenal tissues of cortical (n = 23) and medullary (n = 10) origin. Renin, prorenin, and angiotensinogen levels were also measured. Renin concentrations in normal and pathological adrenals were around 30-fold higher than those in the plasma of normal subjects, except for a Cushing's adenoma, which contains an extremely high renin content. Renin accounted for 56% of the total renin in normal adrenals and up to 87% in neoplastic tissues. This high proportion of renin indicates a likely conversion of prorenin to renin within these tissues. Renin mRNA was detected in each group of adrenal tissues. There was a significant correlation between the concentration of renin and its mRNA (r = 0.75; P less than 0.05). Angiotensinogen and its mRNA were detected in all normal and pathological adrenals. Compared to normal adrenal tissues, the relative amount of angiotensinogen mRNA was significantly higher in pheochromocytomas. However, the increased mRNA level in these tissues was not accompanied by a parallel increase in tissue angiotensinogen levels. Since the translational efficiency of angiotensinogen was verified by in vitro cell-free translation, the low level of angiotensinogen compared to the relatively high amount of its mRNA suggests a lack of storage of this protein in adrenal cells, as in liver cells. This study demonstrates that renin and angiotensinogen are coexpressed in normal and pathological tissues. Tissues of different cellular origin (zona glomerulosa, fasciculata, and medullary tissue), were able to express, store, and process renin and synthesize angiotensinogen. There was no obvious relationship between the expression of these proteins and the pathophysiology of the adrenal gland.

Adrenal Gland Diseases↗
PubMed1989

A defective beta-hydroxylation of dopamine may precede the full development of hypertension in spontaneously hypertensive rats.

A possible mechanism of the previously observed increased adrenal dopamine release and tissue content in spontaneously hypertensive rats (SHR) was explored. The following changes in dopamine beta-hydroxylase activity and catecholamines were noted. At age four weeks (normotensive) or 12 weeks (hypertensive), SHR had lower dopamine beta-hydroxylase activity in the adrenals, heart ventricle and spleen than Wistar Kyoto rats. Tissue dopamine beta-hydroxylase activity in Wistar Kyoto rats was increased with age in the atria but decreased in the ventricles and did not change in the spleen. SHR also had reduced right heart atrial dopamine beta-hydroxylase activity in the hypertensive stage and an overall increase in atrial dopamine content even in the prehypertensive state compared to Wistar Kyoto rats. The increase in noradrenaline content seen with age in the right atrium and spleen in Wistar Kyoto rats was not found in SHR, possibly because of concomitantly decreased dopamine beta-hydroxylase activity. An augmented dopamine:noradrenaline ratio in the spleen of hypertensive SHR may also have been related to an abnormality of the synthesis of noradrenaline from dopamine not necessarily reflected by tissue dopamine beta-hydroxylase determination. A defect of beta-hydroxylation, partly attributable to deficient dopamine beta-hydroxylase activity, may thus precede hypertension and contribute to the hyperdopaminergic state found in SHR.

Adrenal Glands↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Contrasting dopaminergic patterns in two forms of genetic hypertension.

Dopaminergic mechanisms in genetic hypertension were explored via the measurement of catecholamine (CA) turnover, tissue concentration and urinary excretion of dopamine (DA) and its metabolites. In salt-sensitive (S) Dahl rats, the tissue concentration and urinary excretion of DA and its metabolites were decreased in response to salt loading, while adrenal dopamine-beta-hydroxylase (D beta H) activity and aldosterone responsiveness to angiotensin II (A II) were increased. In contrast, spontaneously-hypertensive rats (SHR) showed elevated tissue levels and urinary excretion of DA and its metabolites, adrenal DA turnover and ganglionic DA generation following cholinergic stimulation, but D beta H activity and aldosterone responsiveness to A II were diminished. These two patterns, the hypodopaminergic state in Dahl S rats and the hyperdopaminergic state in SHR, account for two distinct mechanisms of hypertension and precede its development. We detected striking dopaminergic activity-related similarities between Dahl S rats and low-renin essential hypertension (EH) on the one hand, and SHR and non-modulator EH patients on the other.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Hormonal correlates of the inadequate natriuretic response to salt loading in idiopathic edema.

The purpose of this study was to evaluate the body fluid and hormonal responses to salt loading in patients with idiopathic edema. In response to a combined intravenous and oral salt loading, patients with idiopathic edema were found, compared to control women, to have more weight gain, an increase in systolic and diastolic blood pressure, lower excretion of sodium and free dopamine (both the latter being partially accounted for by a diminished salt loading-induced increase in the creatinine clearance), and less plasma dopamine-beta-hydroxylase suppression. There were, between the groups, no differences in plasma and urinary concentrations of the dopamine precursor (dihydroxyphenylalanine), metabolites (dihydroxyphenyl-acetic and homovanillic acid, methoxytyramine and dopamine sulfate), or suppressibility of hormones which are under a partial dopaminergic inhibitory control (plasma renin activity, aldosterone and norepinephrine) by high salt. The inappropriate sodium retention, weight gain, and blood pressure increase following salt loading in idiopathic edema is thus associated with a blunted increase in the glomerular filtration and urinary dopamine excretion rates, as well as plasma dopamine-beta-hydroxylase non-suppressibility by saline. Some circumstantial evidence suggests that the dopamine deficiency is part of a wider disturbance within the cascade of natriuretic hormones.

3,4-Dihydroxyphenylacetic Acid↗
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

Improved liquid chromatographic determination of dopamine-beta-hydroxylase activity in tissues and plasma.

We describe a new assay for dopamine-beta-hydroxylase (D beta H) activity in human and rat plasma and rat tissues using reversed-phase high-performance liquid chromatography with electrochemical detection. Human and rat plasma D beta H activity was measured directly, without extraction of the enzyme. The D beta H from rat tissues was extracted on Concanavalin A-Sepharose before the assay to avoid interference from the presence of tissue catecholamines. Dopamine, the natural substrate of D beta H, was utilized at optimal (enzyme-saturating) concentration. The reaction product, norepinephrine, was isolated on Dowex AG 50W-X4 (H+ form) column. An internal standard, [3H]norepinephrine, was included to correct for the loss of norepinephrine during the procedure. This method allows for the first time the determination of D beta H activity in small volumes of rat and human plasma (5-20 microliters) and tissues. The procedure can be easily set up in any laboratory equipped with a high-performance liquid chromatograph, an electrochemical detector, and a liquid scintillation counter.

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

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↗
PubMed1986

Sympathomedullary activity in one-kidney, one clip hypertensive rats.

In order to evaluate more directly the implications of the sympatho-adrenal system in one-kidney, one clip hypertension (1K1C), we studied adrenal catecholamine synthesis after a bolus injection of 3H-tyrosine, tissue norepinephrine and dopamine concentrations, as well as the urinary excretions of norepinephrine, epinephrine, dopamine and those of the major dopamine metabolites, dihydroxphenylacetic acid (DOPAC) and homovanillic acid (HVA) in 1K1C and control uninephrectomized rats. When compared with controls, the hypertensive rats had a markedly enhanced formation of adrenal 3H-norepinephrine and 3H-epinephrine, higher urinary norepinephrine and epinephrine excretions but lower heart and kidney content of norepinephrine and dopamine as well as decreased urinary excretions of the main dopamine metabolites, DOPAC and HVA. These data suggest an increased norepinephrine and epinephrine synthesis in 1K1C hypertensive rats associated with dopamine synthesis, which is normal but probably disproportionally low relative to the synthesis of norepinephrine and epinephrine. This abnormality may be an important pathogenetic factor in this model of experimental hypertension.

Adrenal Glands↗
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↗