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Biomedical subjects

O Kuchel

Publications and source records attributed to O Kuchel.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Hypertension in hyperthyroidism: is there an epinephrine connection?

Since hypertension seen in euthyroid subjects with depressed conjugated epinephrine and moderately elevated free epinephrine in plasma is strikingly similar to the beta-hyperadrenergic, high-output hypertension seen in some hyperthyroid patients, the possibility is discussed that thyroid action on sulfoconjugation could affect the biodisposability of endogenous free E and so indirectly the manifestation of sympathetic hyperactivity. There is only circumstantial evidence for such a possibility at present. Differences in the conjugation system may be operative in dealing with endogenous as well as exogenous catecholamines. If the latter are used in evaluating the adrenergic receptor reactivity, this may result in incorrect dose-response curves if the concentrations of catecholamines remaining free following infusion are not monitored. The conjugation of catecholamines, E in particular, is a variable which has to be taken account of in the investigation of catecholamine-like manifestation of T3 and T4 excess and in the evaluation of adrenergic influences on thyroid function.

Blood Pressure↗
PubMedDate not supplied

An atrial natriuretic factor-like activity in rat posterior hypophysis.

An atrial natriuretic factor-(ANF) like immunoreactivity (IR-ANF), is present in the posterior hypophysis of the rat. In order to obtain more direct information on the presence and biological activity of this new posterior hypophysis peptide, we applied a procedure similar to that described for rat atria, to extract an ANF-like material from the posterior hypophysis of the rat. An analysis of the tissue extracts by reverse-phase high performance liquid chromatography (RP-HPLC) suggested that, in this organ, the ANF-like peptides may be present in multiple forms: a low molecular weight peptide which had a RP-HPLC pattern similar to that of the synthetic rat 28 amino acid C-terminal (Ser 99-Tyr 126) ANF, and an unidentified higher molecular weight peptide. The partially purified low molecular weight peptide was found to have a potency similar to that of synthetic rat ANF in the inhibition of adrenocorticotropin-stimulated aldosterone secretion in dispersed zona glomerulosa cells, suggesting that the ANF-like peptide was biologically active. Immunohistochemical visualization of the ANF-like peptides revealed the distribution of the peptide within the posterior hypophysis. There was no immunohistochemical staining for ANF in the intermediate lobe. These results suggest the existence of biologically active ANF-like peptides within the posterior hypophysis of the rat. It is possible that these peptides may modulate locally the posterior hypophysis hormone secretion.

Adrenal Glands↗
PubMedDate not supplied

Atrial natriuretic factor in the spinal cord of normotensive and hypertensive rats.

Atrial natriuretic factor (ANF) was investigated in the rat spinal cord and hypothalamus using two radioimmunoassays. ANF was also quantified in both tissues of Spontaneously Hypertensive Rats and Dahl rats. Spinal cord and hypothalamus were found to be immunoreactive to proANF and its near-NH2- or near-COOH-terminal fragments. A major part of the extracted ANF was a COOH-terminal peptide smaller than or the same as ANF (Ser99-Tyr 126). SHR had higher hypothalamic and spinal cord ANF concentrations than Wistar Kyoto rats, while the Dahl salt-sensitive animals exhibited an increase in spinal cord ANF when compared with the Dahl salt-resistant group. The data suggest that spinal cord may produce ANF locally with processing similar to that in hypothalamus. Changes in ANF concentrations occurring during the course of hypertension remain to be further investigated.

Animals↗
PubMedDate not supplied

Effect of prolonged high salt intake on atrial natriuretic factor's kinetics in rats.

Plasma atrial natriuretic factor (ANF) paradoxically decreases after 5 weeks (but not after 3 weeks) of 8% NaCl intake in normotensive rats. As this phenomenon remains unaccounted for by changes in ANF production, we studied the disappearance of [125I]ANF(99-126) from the circulation as an alternative explanation of plasma ANF decline. Following 5 weeks (but not 3 weeks) of an 8% NaCl diet, plasma concentrations of [125I]ANF were significantly decreased and metabolic clearance rate and volume of distribution were increased compared to control rats fed a 0.8% NaCl diet. By studying [125I]ANF tissue uptake we noted significantly greater peptide uptake after 5 weeks (but not after 3 weeks) of high salt consumption in several tissues. We hypothesize that prolonged (at least 5 weeks) 8% NaCl ingestion increases the density and/or affinity of ANF binding sites. These changes may be responsible for the previously observed decline in plasma ANF concentrations after a prolonged high salt intake.

Animals↗
PubMedDate not supplied

An increase in urinary catecholamines of renal origin in patients with "borderline" hypertension.

Plasma and urinary catecholamines (norepinephrine and epinephrine) and urinary dopamine excretion were studied in 45 essential hypertensive patients subdivided into borderline (labile) and stable hypertension. Borderline hypertensive patients had a higher mean fractional renal clearance of catecholamines (the clearance of catecholamines relative to creatinine clearance) than both control subjects and stable hypertensive patients. A significantly positive correlation between the renal clearance of catecholamines and urinary dopamine excretion was also found in those with borderline hypertension, but not in control subjects or those with stable hypertension. These data indicate that patients with borderline hypertension have a relatively exaggerated renal catecholamine release. They probably reflect an increased sympathetic discharge to the kidney in "borderline" hypertension, occuring to a lesser degree in stable hypertension and control subjects. Thus, urinary catecholamine measurements do not specifically reflect the level of circulating catecholamines, particularly in borderline hypertension.

Adult↗
PubMedDate not supplied

Labetalol in essential hypertension.

Labetalol is an orally active adrenoreceptor-blocking drug which is a competitive antagonist of both alpha- and beta-adrenoreceptor sites. Thirty patients with essential hypertension were admitted to the study. The mean of initial systolic and diastolic blood pressures of these patients was 160/101 +/- 3/1 supine and 155/104 +/- 3/1 mm Hg standing, and the mean blood pressures at the end of the 16 week trial was 142/90 +/- 4/2 supine and 131/91 +/- 3/2 mm Hg standing. The average dose of labetalol was 546 mg: eight patients received a dose of 300 mg, seven a dose of 600 mg, six a dose f 900 mg, and two a dose of 1,200 mg. The patients who needed the highest doses of labetalol had an initial lowering of their blood pressures followed by a gradual increase despite the higher doses of labetalol. There was no significant change in the mean peripheral renin activity value. Side effects were reported by 18 of the 30 patients, but only 1 patient withdrew for this reason. Two patients were considered to be treatment failures. Overall, labetalol was found to be an effective antihypertensive agent in 15 patients.

Adult↗
PubMedDate not supplied

Adrenergic and dopaminergic properties of dopamine sulfoconjugates.

UNLABELLED: The 3- and 4-sulfate esters of dopamine (DA-3-SO4 and DA-4-SO4, respectively), the two main metabolites of DA, were evaluated for potential intrinsic or indirect catecholaminergic activities. Both compounds lacked any appreciable affinities for alpha 1, alpha 2, beta 1, beta 2 and DA-2 receptors. In the superfused [3H]norepinephrine-preloaded dog saphenous vein, both dopamine sulfates were devoid of any intrinsic inhibitory activity such as observed with dopamine pre- and postsynaptically. In addition, they did not displace the labeled vesicular neurotransmitter as did dopamine. In anesthetized dogs the two compounds failed to stimulate either the dopaminergic receptors (DA-1) of mesenteric vascular beds or the adrenergic receptors mediating the vasodilatory and pressor responses to dopamine. CONCLUSION: In our experimental conditions DA-3-SO4 and DA-4-SO4, the products of dopamine sulfoconjugation, lacked any demonstrable intrinsic affinity and/or efficacy on the dopaminergic and adrenergic receptors directly or indirectly through their metabolic transformation or through displacement of endogenous neurotransmitter.

Animals↗
PubMedDate not supplied

Contribution of the sympathetic nervous system to the centrally-induced pressor action of angiotensin II in rats.

1. Angiotensin II (ANG II) may increase blood pressure by central nervous system mechanisms. The involvement of the sympathetic nervous system in the centrally-induced pressor effect of ANG II in the rat was investigated. 2. Plasma noradrenaline concentrations, measured as an index of sympathetic nervous system activity, increased after intracerebroventricular (i.c.v.) injection of pressor doses of ANG II, both in normotensive and in spontaneously hypertensive rts. 3. To assess the functional significance of this, the sympathetic nervous system was inhibited by phentolamine, reserpine, and guanethidine. In phentolamine-infused rats, low doses of i.c.v. ANG II elicited a blood pressure decrease, but at maximal pressor doses, no difference between phentolamine-treated and control rats was observed. In reserpinized rats, the central pressor effect of ANG II was greater than in controls. Guanethidine pretreatment did not affect the blood pressure response to i.c.v. injected ANG II. 4. It is concluded that the central pressor effects of ANG II are accompanied by a stimulation of the sympathetic nervous system. In the rat, this stimulation may be functionally important for the initial phase of the central pressor action. This could not be established for the maximal pressor responses.

Angiotensin II↗
PubMedDate not supplied

Unconjugated hyperepinephrinemia: a hallmark of hypertension imitating pheochromocytoma?

Hypertensive patients with elevated and hyperresponsive plasma norepinephrine and epinephrine (NE + E) associated with low conjugated NE + E were previously identified by determination of the sum of NE + E. Because of their excessive E but not NE responses to glucagon and also hypertension corresponding to E excess, we explored whether an elevated unconjugated E resulting from a selective E conjugation defect could be obscured by the sum of NE + E. We found that nine patients with elevated E (reflected by the normal 4:1 ratio of plasma NE to E reversed in favor of E), had, when compared to 31 patients with plasma NE exceeding E:1) lower plasma conjugated E (mean 0.03 vs 0.27 ng/ml, p less than 0.01), lower degree of E conjugation (8 vs 51%, p less than 0.01), and a higher maximum systolic (p less than 0.05), pulse pressure (p less than 0.02) and higher pulse rates (p less than 0.04), but no differences in the unconjugated and conjugated proportions of plasma NE; and 2) an absence of conjugated E throughout the circulation and relative preponderance of E over NE at sampling points close to the peripheral venous blood (p less than 0.05). The absolutely and relatively decreased plasma conjugated E in patients with E exceeding NE (without difference in conjugated NE) is a preliminary indication that a selective sulfoconjugating defect of E results in plasma E higher than NE in accordance with the hyper-beta-adrenergic features of their hypertension. Epinephrine, a circulating hormone, is more dependent on conjugated E reflect better this defect than those measuring the sum of NE and E.

Adolescent↗
PubMedDate not supplied

Sulfoconjugation of catecholamines, nutrition, and hypertension.

Sulfoconjugation is an important metabolic pathway determining the fate and potential cardiovascular action of ingested phenolic substances. Among the three catecholamines, dopamine (DA) is to the highest degree sulfoconjugated and has the highest affinity toward the phenolsulfotransferase (PST). The concentration of some sulfated catecholamines, particularly of DA sulfate, increases following ingestion of catecholamines or their precursors. This can be confounded with blood-derived increases in DA sulfate associated with BP peaks in some hypertensive patients. We mimicked, therefore, the latter condition by infusion of free DA into normotensive subjects. At low DA infusion rates, plasma DA sulfate exceeded free DA concentrations, and there were no changes in blood pressure and pulse rate. At higher DA infusion rates, blood pressure and pulse rate increased only while plasma free DA concentrations exceeded those of DA sulfate, indicating that free DA remains biologically active only prior to being conjugated. A similar increase in DA sulfate from alimentary sources (e.g., eating a banana) remains without cardiovascular response and is not associated with an overflow of free DA, since all the ingested DA is conjugated in the gut. We describe a patient with pheochromocytoma who experienced repeated hypertensive crises after ingestion of food containing some biogenic amines, (once also documented by NE increase), possibly due to a phenol sulfoconjugation defect (e.g., substrate inhibition of the PST or its genetic deficiency). Platelet PST-determinations may serve as a screening tool to detect subjects with sulfoconjugation defects since they probably reflect the PSt activity in the gut where ingested phenols are sulfoconjugated.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Dopamine surges in hyperadrenergic essential hypertension.

From a total of 61 referred hypertensive patients, 21 were clinically suspected of pheochromocytoma but in none was this diagnosis confirmed. Instead we found nine of the 21 patients had surges of conjugated dopamine during hyperadrenergic periods unaccounted for by rise in norepinephrine (NE) or epinephrine (E). Overall, essential hypertensive (EH) patients had in plasma (ng/ml) higher conjugated dopamine (DA) (2.3 +/- 0.2 vs 1.0 +/- 0.1, p less than 0.01), increasing with age (p less than 0.01), lower conjugated NE + E (0.6 +/- 0.1 vs 1.2 +/- 0.2, p less than 0.01), and higher free E (p less than 0.007), lower urinary free DA and total DA but higher free NE + E excretions (each p less than 0.05) than 24 control subjects. Following the DA surges, a short-lived urinary overflow of total DA occurred. The patients with DA surges were older, had a higher incidence of low conjugated NE + E (less than 0.23 ng/ml), a higher proportion of arterial free DA, and higher venous baseline conjugated plasma DA than the rest of the patients. Patients with low conjugated NE + E had in turn higher plasma DA concentrations at several regional sampling sites than patients with normal conjugated NE + E. High conjugated DA in EH probably results from pulsatile DA surges leading to a rise of baseline plasma conjugated DA. In the short run DA pulses can result in temporary alpha- and beta-adrenergic actions of huge arterial free DA concentrations prior to DA conjugation; in the long run the excessive high affinity DA conjugation may take preference to the lower affinity NE and lowest affinity E conjugation and free E increases. Both result in an acute or chronic increase of sympathetic tone.

Adolescent↗