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Biomedical subjects

O Kuchel

Publications and source records attributed to O Kuchel.

At least 73 records · Page 4Linked to original sources
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

Effects of atrial natriuretic factor on natriuresis and cGMP in patients with essential hypertension.

Human atrial natriuretic factor (h-ANF) or its vehicle only, were infused at rates of 0.8, 1.6 and 3.2 micrograms/min over three successive 30-min periods, into five patients with mild essential hypertension and seven normotensive controls. Baseline (mean +/- s.e.m.) plasma ANF levels were 13 +/- 2 in patients and 8 +/- 1 pg/ml in controls. During the first period, plasma ANF and cyclic guanosine monophosphate (cGMP) levels increased in both groups without significant alteration of blood pressure, heart rate, diuresis, natriuresis or cGMP excretion rate. During the second period of infusion, plasma ANF levels increased up to 179 +/- 39 and 177 +/- 30 pg/ml in patients and controls and plasma cGMP concentrations increased X 5.0 and X 4.9, respectively; natriuresis increased X 2.4 in patients and X 3.1 in controls while urinary cGMP increased X 10.9 in patients and X 10.5 in controls. During the last period, three controls became hypotensive while blood pressure remained stable in the other controls and in the patients with essential hypertension. During this period, the increases in plasma ANF concentration, diuresis, natriuresis and urinary cGMP excretion were similar in both groups. However, the mean plasma cGMP concentration after 90 min infusion was significantly higher in hypertensive patients than in control subjects (30.7 +/- 3.3 versus 15.6 +/- 3.4 pmol/ml, P less than 0.05). The half-life and clearance of plasma ANF, upon discontinuation of the infusion, were similar in both groups. Our data suggest that patients with mild essential hypertension have enhanced increases in plasma cGMP but normal increases in diuresis, natriuresis and cGMP excretion following infusion of h-ANF at pharmacological rates.

Adult↗
PubMed1987

Atrial natriuretic factor (ANF) in experimental and human hypertension.

The plasma levels of immunoreactive (IR)-ANF have been evaluated by radioimmunoassay in several models of experimental hypertension and in human hypertension. In all models of experimental hypertension so far studied, the plasma levels of IR-ANF are consistently increased. This is accompanied by a decrease, at certain time intervals, of the IR-ANF levels in the left atrium. In human essential hypertension, the plasma levels of IR-ANF are not increased except in the severe form (diastolic blood pressure above 110 mmHg). In renovascular hypertension, the peripheral levels of IR-ANF are not different from the normal levels but are increased above normal in aortic blood.

Animals↗
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↗
PubMed1986

Handling of dopamine and dopamine sulfate by isolated perfused rat kidney.

The possible contribution of circulating dopamine sulfate to urinary free dopamine and the synthesis of norepinephrine by the renal nerves were examined in the isolated perfused rat kidney. Perfusion of the kidney with dopamine sulfate did not yield significant amounts of free dopamine indicating that, unlike L-dopa, dopamine sulfate is not a good source of urinary free dopamine. The excretion of dopamine sulfate was slower than or comparable with that of free dopamine, suggesting that sulfoconjugation is not a mechanism to facilitate the excretion of free dopamine. Unlike free dopamine, dopamine sulfate was not metabolized by renal catechol-O-methyltransferase or monoamine oxidase. Perfusion of L-dopa and free dopamine led to the generation of norepinephrine in the kidney. This synthesis was abolished when the kidney was denervated, suggesting that the renal nerves were the main sites of the norepinephrine synthesis. Both norepinephrine and dopamine were rapidly metabolized by catechol-O-methyltransferase and monoamine oxidase, but renal phenolsulfotransferase appeared to have no action on the catecholamines.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Metabolism and storage of catecholamines in rats with pheochromocytoma implants.

New England Deaconess Hospital rats implanted with a pheochromocytoma P259 became hypertensive and showed high concentrations of plasma dopamine (42.0 +/- 14.6 ng/ml) and norepinephrine (45.7 +/- 8.4 ng/ml). However, the norepinephrine content of several peripheral tissues of these rats did not differ from those of the New England Deaconess Hospital control rats, and their dopamine content, although slightly higher, was much lower than would have been expected from the plasma dopamine levels. Methylation by catechol-O-methyltransferase did not appear to play a major role in the inactivation of tissue catecholamines since there were no noticeable increases of normetanephrine or 3-methoxytyramine in the tissues of the rats with pheochromocytoma. There was also no increase in conjugated dopamine, in either the sulfate or glucuronide form, in the plasma or tissue of the hypertensive rats, although injection of L-dopa induced a large increase in dopamine sulfate in the plasma and urine of these rats. This finding indicated that, although their sulfoconjugation mechanism was intact and not affected by the pheochromocytoma, it did not participate in the metabolism of dopamine released by the tumor into the blood. On the other hand, plasma and urine of tumor-bearing rats exhibited abnormally high concentrations of homovanillic acid, the main metabolite of dopamine resulting from monoamine oxidase action. In contrast to the control rats, intravenous infusion of free dopamine in rats with pheochromocytoma had no effect on plasma free dopamine levels but increased homovanillic acid levels considerably. The present data underline the important role of monoamine oxidase in the removal of excessive quantities of catecholamines released by the tumor in New England Deaconess Hospital rats with the pheochromocytoma implant.

Adrenal Gland Neoplasms↗
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

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↗