Search PubMed⌕ Search

Biomedical subjects

O Kuchel

Publications and source records attributed to O Kuchel.

At least 109 records · Page 6Linked to original sources
PubMed1984

Regional distribution of free and sulfoconjugated catecholamines in the bovine adrenal cortex and medulla.

The intraadrenal distribution of free and sulfoconjugated catecholamines and the activity of the catecholamine sulfoconjugating enzyme phenolsulfotransferase in the bovine adrenal gland are described. In the adrenal cortex all three free catecholamines, epinephrine, norepinephrine, and dopamine, were detected in various concentrations. In the adrenal medulla, the relative proportion of the main adrenal catecholamines, free epinephrine and free norepinephrine, was found to be higher in the medullary sections derived from the subcortical areas where the ratio of epinephrine to norepinephrine was 8:1 than in the centre of the organ where norepinephrine levels reached those of epinephrine. Free dopamine, representing about 1.0% of the total catecholamine content was distributed in the same pattern as epinephrine or the sum of epinephrine and norepinephrine, revealing a significant positive correlation between regional dopamine and epinephrine plus norepinephrine (r = 0.97) as well as between dopamine and epinephrine (r = 0.96). Phenolsulfotransferase activity was present in both medulla and cortex. Dopamine sulfate was detected in relatively small concentration in all cortical and medullary layers, but norepinephrine sulfate and epinephrine sulfate were not present. The meaning of this distribution of individual catecholamines and phenolsulfotransferase activity in both cortex and medulla is discussed.

Adrenal Cortex↗
PubMed1984

Dopamine 3-sulfate inhibits aldosterone secretion in cultured bovine adrenal cells.

It has been demonstrated that dopamine inhibits the aldosterone (Aldo) secretion in bovine adrenal cells in vitro. Because the majority of the total circulating dopamine (DA) in bovine plasma (72%) is present in sulfoconjugated form (6.8 +/- 3.4 pmol/ml) and free DA, DA sulfate, and phenolsulfotransferase (PST) activity can be found in the bovine adrenal cortex, we examined whether the inhibitory action of free DA on angiotensin II- (ANG II) stimulated Aldo secretion by cultured bovine adrenal cells can also be reproduced by sulfoconjugated DA analogues. Cells from the bovine adrenal glands cultured for 3 days before testing responded to 10(-8) M ANG II stimulation by a 10- to 12-fold increase in Aldo output. This stimulatory effect was partially inhibited by the addition of free DA and DA 3-sulfate, whereas DA 4-sulfate was inactive. Both free DA and DA 3-sulfate produced their maximal inhibitory effect at a concentration of 100 microM, with a decrease in Aldo secretion by 61% (free DA) and 44% (DA 3-sulfate). The slightly different inhibition curves for DA and for DA 3-sulfate on Aldo secretion cannot be explained by liberation of free DA through hydrolytic processes because less than 1% free DA was detected after the incubation of the cells with sulfoconjugated DA. These in vitro findings suggest that DA 3-sulfate may be effective in complementing the dopaminergic inhibition of Aldo secretion at the adrenal level.

Adrenal Glands↗
PubMed1984

A new method for the simultaneous analysis of free and sulfoconjugated normetanephrine, metanephrine, and 3-methoxytyramine in human urine by HPLC with electrochemical detection.

A sensitive and specific assay for free and sulfoconjugated normetanephrine, metanephrine, and 3-methoxytyramine was achieved by tetraphenylboron complexing and by high-performance liquid chromatography with electrochemical detection. Sulfoconjugated metabolites were hydrolyzed by sulfatase. Complexing the 3-O-methylated catecholamines with tetraphenylboron followed by their extraction in either and reextraction in dilute hydrochloric acid succeeded in partially purifying the sample without the use of a prepacked column. Detection by electrochemical technique additionally eliminates unoxidable components in the urine. The relatively high sensitivity of this method permits measurement of metabolite concentrations as low as 10 ng/ml, allowing for the first time the determination of free 3-O-methylated catecholamines in human urine. Hydrolysis by sulfatase specifically identifies the form of the conjugated metabolite. The mean total (free plus sulfoconjugated) values of normetanephrine, metanephrine, and 3-methoxytyramine obtained from 25 normal volunteers were 214, 102, and 227 micrograms/day, respectively. Values were greatly increased in patients with pheochromocytoma. The degree of sulfoconjugation varied, and each individual metabolite was highest with normetanephrine (86%). This method is sensitive, rapid, simple, and can be easily standardized for clinical investigation of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1984

Catecholamine sulfates and platelet phenolsulfotransferase activity in essential hypertension.

Because of high plasma concentrations of conjugated catecholamines and their unknown relationship to hypertension, we determined those conjugates more specifically as catecholamine sulfates together with the sulfoconjugating enzyme-phenolsulfotransferase activity in platelets of 62 patients with essential hypertension and 32 normal controls. Our results indicated: (1) that the pool of total (free and sulfated) catecholamines (dopamine, norepinephrine, and epinephrine) is higher (because of an increase in dopamine sulfate levels) but the degree of epinephrine conjugation is lower in patients with essential hypertension compared with controls; (2) that norepinephrine sulfate levels rise with age in both groups, but the increase in free norepinephrine with age observed in controls was not observed in patients with essential hypertension; and (3) that catecholamine conjugates were found to be exclusively sulfates and platelet phenolsulfotransferase activity was not different in both groups. Platelet phenolsulfotransferase activity was, however, positively correlated with plasma norepinephrine sulfate levels, and the degree of sulfoconjugation of norepinephrine was positively correlated with that of dopamine in controls but not in patients with essential hypertension. These abnormalities occurring in essential hypertension in the absence of intergroup differences in platelet phenolsulfotransferase activity suggest that the enzyme is either not a good marker of the overall activity or that other factors account for the observed differences. Thus, additional determinants of the process of generation and degradation of sulfoconjugated catecholamines, some of which may be more stable markers of sympathetic activity than free catecholamines, need to be explored.

Adult↗
PubMed1984

The adrenal synthesis and tissue content of dopamine increase when the blood pressure rises in spontaneously hypertensive rats.

Hypertensive (eight-week-old) but not normotensive (four-week-old) spontaneously hypertensive rats (SHR) have a higher adrenal dopamine (DA) synthesis and release, DA concentration in adrenals and kidney and urinary excretion of DA, dihydroxyphenylacetic acid and methoxytyramine than control WKY rats. At age 14 weeks, with progressive hypertension, the heart atria and ventricle DA content also increases. These abnormalities remain unaccompanied by changes in norepinephrine and epinephrine. Increased DA release, tissue content and urinary excretion of DA and its metabolites are thus selectively involved in the sequence of events leading to hypertension in SHR.

Adrenal Glands↗
PubMed1983

Catecholamine glucuronidation: an important metabolic pathway for dopamine in the rat.

In the present study, we found that large quantities of dopamine (DA) glucuronide were present in rat cerebrospinal fluid (CSF), plasma, and urine, whereas the glucuronides of norepinephrine (NE) and epinephrine (E) were almost undetectable. The high urinary excretion of DA glucuronide was in a range comparable to that of homovanillic acid (HVA). Sulfates of DA, NE, and E were measurable in all three body fluids, but only in small quantities. The measured DA glucuronide was predominantly of endogenous origin, as the feeding of sucrose instead of routine diet did not reduce the urinary output of DA glucuronide. Adrenalectomy but not peripheral sympathectomy induced by chronic guanethidine injection substantially decreased plasma DA glucuronide concentrations, indicating that the adrenals serve as an important source of endogenous DA glucuronide. The data suggest that glucuronidation constitutes an important metabolic pathway for endogenous DA of central and peripheral origin in rats; this route, however, is exclusive to DA and appears to play a negligible role for NE and E.

Animals↗
PubMed1983

Changes of catecholamines in central and peripheral tissues and in the urines of deoxycorticosterone--salt hypertensive rats.

The catecholamine concentrations in the urines and in the tissues of the kidney, heart, striatum, and hypothalamus of control rats and rats treated with deoxycorticosterone and salt for 2-week and 5-week periods were measured and compared. In 2-week-treated rats there were no changes in blood pressure and catecholamines. In 5-week-treated rats, the blood pressure increased from 117 +/- 5 to 152 +/- 5 mmHg (1 mmHg = 0.13 kPa) and there was an increase of urinary dopamine, norepinephrine, and epinephrine. The kidney and heart tissues of the hypertensive rats showed a decrease of norepinephrine while in the hypothalamus all three catecholamines were increased. These data suggest that dopamine and epinephrine may also be involved in the sympathetic dysfunction in deoxycorticosterone--salt hypertension. They demonstrate for the first time an increase of dopamine, norepinephrine, and epinephrine in the hypothalamus of deoxycorticosterone--salt hypertensive rats.

Animals↗
PubMed1983

Conjugated catecholamines and their measurement: some pharmacokinetic aspects.

Comparison of the methods of determination of conjugated catecholamines shows that, despite their variable absolute values, the relative proportions of the free and conjugated dopamine, norepinephrine and epinephrine are close (mean of 97.3% of dopamine, 73% of norepinephrine and 84% of epinephrine being conjugated) and these proportions remain similar whether acid or sulphatase hydrolysis is used. Thus, the variability is due rather to the methods of catecholamine determination than to the mode of hydrolysis of conjugated catecholamines. The measurement of dopamine sulphate, which is preferable to non-specific measurements, is a useful tool in detecting individual differences of sulpho-conjugation in subjects who sulphoconjugate dopamine with a delay and are thus more prone to experience, prior to dopamine sulphoconjugation, cardiovascular and other actions of dopamine not seen in subjects who sulphoconjugate dopamine immediately.

Catecholamines↗
PubMed1983

Dopamine: an important neurohormone of the sympathoadrenal system. Significance of increased peripheral dopamine release for the human stress response and hypertension.

In human plasma, the concentration of free dopamine (DA) is approximately equal to that of epinephrine (E). Like norepinephrine (NE) and E its concentration may increase during physical effort and stress (Fig. 1). Most of the stress-related increase in plasma DA is derived from peripheral noradrenergic nerve terminals and the adrenal medulla. Because virtually all of the DA is rapidly conjugated upon release, it is necessary to measure plasma total (free + conjugated) DA. When dietary sources are controlled, the total DA concentration can be used as an indicator of the intensity of the sympathetic response and possibly the level of training in animals and humans. In normal individuals, plasma DA and blood pressure (BP) are usually negatively correlated since during a low level sympathetic discharge the hypotensive action of DA via dopaminergic vascular receptors predominates. The DA action on BP is, however, biphasic and dependent on its concentration. In many hypertensive patients, hypertensive peaks, which cannot be accounted for by rises in NE and E, are associated with very large stimulus-elicited increases in total DA into a range in which its hypertensive action via beta and alpha-receptors could temporarily predominate. Alternatively, this rise in DA could be a marker of the sympathetic discharge or a negative modulator of other hypertensive influences rather than the cause of the elevated BP. In primary aldosteronism, there is a more sustained increase in circulating DA. In both groups of patients the DA levels decrease with successful treatment. Concentrations of total DA and of free + conjugated NE + E in plasma are a more sensitive measure of sympathetic activity than are levels of free catecholamines, and they may provide a clinically useful biochemical index for categorizing hypertension and following its treatment.

Adrenalectomy↗
PubMed1983

Differential effects of a low dose dopamine infusion on prolactin secretion in normal and hyperprolactinemic subjects.

The PRL inhibitory effect of dopamine (DA) in human in vivo studies has been previously demonstrated with DA infusions at rates generally exceeding 2 micrograms/kg . min. We report here the effects of a DA infusion administered at a rate of 0.02 microgram/kg . min for 180 min to 10 normal subjects and 25 hyperprolactinemic patients with pituitary tumors (13 microprolactinomas, 8 macroprolactinomas, and 4 expanding nonsecreting pituitary adenomas). Serum free DA concentrations during the 3-h DA infusion reached an average of 0.8 +/- 0.1 ng/ml (about an 8- to 10-fold rise from basal levels). DA produced a significant (P less than ) 0.001) decline in plasma PRL levels in both normal subjects and hyperprolactinemic patients. There was a negative linear correlation between the serum DA concentrations and the percent PRL variation from basal levels (r = -0.58; P less than 0.001). The comparison of RPL responses between the different groups revealed that the mean percent overall PRL inhibition was significantly lower in patients with microprolactinomas than in normal subjects (P less than 0.02). On the other hand, PRL inhibition was greater in patients with nonsecreting adenomas than in either patients with microprolactinomas or those with macroprolactinomas (P less than 0.001). From 90-180 min, PRL suppression was also greater in patients with nonsecreting adenomas than in normal controls (P less than 0.05). The present study shows that 1) slight elevations of plasma DA are sufficient to inhibit PRL secretion, suggesting that DA acts as major physiological PRL-inhibiting factor, 2) there is a relative PRL resistance to DA inhibition in microprolactinoma patients; and 3) PRL is hyperresponsive to DA in expanding nonsecreting pituitary tumors.

Adenoma↗
PubMed1983

Extrarenal angiotensin-forming enzymes.

There are two types of enzymes in tissues leading to angiotensin formation: a) those resulting in the formation of angiotensin I, such as renin and cathepsin D, the presence of which is now well established for brain tissue and b) Those leading to the direct formation of angiotensin II without the angiotensin I step, such as cathepsin G and tonin. Recent findings concerning tonin, a serine protease, are described: a) 80% of its amino acid sequence, b) its different characteristics from other serine proteases, from renin, cathepsin D and the angiotensin I converting enzyme, c) the activation of inactive renin, d) its involvement in the 1K-1C hypertensive rats, e) the demonstration of its presence in the distal tubular cells of the rat kidney, and finally, f) its presence in urine and the influence of age and of sodium intake on its urinary excretion.

Amino Acids↗
PubMed1983

[Peripheral vascular effects of metoprolol, pindolol and propranolol in hypertensive patients].

Hemodynamic parameters, after administration of three different beta-blockers, were measured in fifteen hypertensive, and five normotensive, subjects. The non-invasive hemodynamic measurements were made prior to drug administration, after the first dose, and after prolonged treatment with either: metoprolol (M) 100 mg b.i.d., propranolol (Pr) 80 mg b.i.d., or pindolol (P) 10 mg b.i.d. With the parameters of blood pressure (B.P.), pulse rate (H.R.), blood flow in the leg at rest were determined with the plethysmographic impedance technique; venous compliance (V.C.), and flow in the leg after reactional hyperemia (F.R.H.) were evaluated by the mercury gauge technique. The pneumoplethysmographic technique was used to measure digital flow (D.F.). During administration of metoprolol, the B.P. and H.R. decreased significantly in the first few hours, and remained so during the prolonged treatment period of 4 weeks; the other parameters did not change significantly. Propranolol, after short-term treatment, decreased H.R. and blood flow in the leg at rest. Also, modifications in the venous compliance occurred but are difficult to interpret. After administration of pindolol, except for a decrease in H.R. and reactional hyperemia that occurred during the 2nd hour, no significant changes occurred in the other parameters. The digital flow showed non-significant variations. These preliminary results demonstrate that the changes registered through non-invasive techniques, although very small, affect pindolol less than metoprolol or propranolol.

Adrenergic beta-Antagonists↗
PubMed1983

Conjugation patterns of endogenous plasma catecholamines in human and rat. A new specific method for analysis of glucuronide-conjugated catecholamines.

Plasma free, sulfoconjugated, and glucuronoconjugated CAs were determined radioenzymatically before and after hydrolysis. CA sulfates and glucuronides were hydrolyzed by sulfatase and Ketodase, respectively. Total CA conjugates were deconjugated by acid lyophilization. On the basis of data obtained from systematical studies on these methods, the conjugation patterns of endogenous plasma CA in human and rat have been qualitatively and quantitatively identified. The results show that (1) in human plasma, sulfation is the sole conjugation mode for DA, NE, and E; (2) in rat plasma, sulfation also occurs in DA, NE, and E but the quantities of the sulfates are small, whereas glucuronidation predominates in DA and occurs exclusively in DA but not in NE and E; (3) in both species, conjugation is preferential for DA rather than NE and E. In this study, a new specific method for analysis of glucuronoconjugated CA has been developed.

Animals↗
PubMed1982

The hemodynamic relevance of free and conjugated dopamine in pheochromocytoma.

Two patients with adrenomedullary hypersecretion (confirmed pheochromocytoma and adrenomedullary hyperplasia) presented 15 spontaneous crises associated with hypertension or hypotension with or without tachycardia. Correlation coefficients calculated between extreme values of pulse rates and of systolic and diastolic blood pressures on the one hand and plasma free and conjugated norepinephrine, epinephrine, and dopamine (DA) sampled at the height of the crises on the other, showed no relationships between free or conjugated norepinephrine or epinephrine and blood pressure or pulse rate. However, plasma conjugated DA was negatively correlated with systolic blood pressures (P less than 0.02) and diastolic blood pressures (P less than 0.03) and free plasma DA was negatively correlated with pulse rates (P less than 0.001). These data suggest that the extremely high circulating level of conjugated DA in pheochromocytoma may, in the presence of high circulating conjugated norepinephrine and possibly high alpha-adrenergic receptor occupancy, decrease blood pressure by its predominant action on dopaminergic receptors while elevated free DA may decrease the tendency to tachycardia, possibly by lowering the venous return.

Adrenal Gland Neoplasms↗
PubMed1981

Basis of false-positive glucagon tests for pheochromocytoma.

In more than half of 67 patients suspected of having pheochromocytoma, glucagon stimulation increased plasma free norepinephrine (NE) and epinephrine (E) 50% or more, with rising blood pressure or pulse rate; only three patients, however, harbored a pheochromocytoma. A low degree of catecholamine conjugation accounts for most of the false-positive results. In patients with low conjugated NE +E there was a greater rise in free NE +E and free E as well as in pulse rate after glucagon stimulation than in those with normal levels of conjugated NE+E. Glucagon-sensitive adenylate cyclase was found in pheochromocytomas but not in a functional adrenocortical adenomas. After sham administration of glucagon, there were rises in blood pressure but not in free NE or E in four patients. The glucagon-induced catecholamine test can be false-positive in hyperadrenergic essential hypertensive patients with abnormally low conjugated NE +E. Saline alone in a sham glucagon test in susceptible patients raises systolic blood pressure and pulse rate, and therefore, if plasma free NE and E are measured and found not to rise this type of false-positive result can be eliminated.

Adenylyl Cyclases↗