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Biomedical subjects

O Kuchel

Publications and source records attributed to O Kuchel.

At least 127 records · Page 7Linked to original sources

Presence of conjugated catecholamines in rat brain: a new method of analysis of catecholamine sulfates.

A new method of measuring catecholamine (CA) sulfate permitted us to detect its presence in rat brain for the first time. The procedure consisted of separating the CA sulfate from the free CA by alumina adsorption followed by passage through Dowex, and measuring the CA sulfate by a radioenzymatic assay in the presence of a sulfatase. This method permitted demonstration of the presence of dopamine sulfate, and occasionally, of norepinephrine and epinephrine sulfate in the hypothalamus, striatum, and hippocampus of rat brain.

Animals↗

Platelet phenolsulfotransferase and catecholamines: physiological and pathological variations in humans.

The phenolsulfotransferase (PST) is the main sulfoconjugating enzyme of catecholamines. We have described a standardized, sensitive, and reproducible method of measurement of PST activity from human blood platelets. The affinity of PST was, in descending order, towards dopamine (DA) greater than norepinephrine (NE) greater than epinephrine (E) (Km (DA) equals 17.6 microM, Km (NE) equals 66.6 microM, Km (E) equal 330 micro M). The optimum pH was found to be 5.9. Platelet PST measurements in 26 subjects led to the following observations, (i) The individual PST activity remains relatively stable during manipulations such as direct venous puncture, upright posture, physical exercise, and consumption of a copious meal. (ii) The mean platelet PST activity was 67 plus or minus 34 (mean plus or minus SD) U/mg protein in men and 43 plus or minus 19 U/mg protein in women. (iii) The platelet PST activity varies during the menstrual cycle with a marked decrease 7-10 days before menstruation. (iv) Essential hypertensive patients, appearing clinically as a syndrome imitating pheochromocytoma, had absent or low conjugated catecholamines. In one of them, no PST activity could be detected in platelets using catecholamines as substrates whereas a considerable activity was present with p-nitrophenol. The potential usefulness of the platelet PST measurements is discussed.

Adrenal Gland Neoplasms↗

The extra-adrenal synthesis of epinephrine in rats. Possible involvement of dopamine sulfate.

Bilaterally adrenalectomized rats were administered [3H]L-dopa, [3H]DA, and [3H]DASO4. Both [3H]L-dopa and [3H]DASO4 were found to generate [3H]E in the urine and kidney tissues of adrenalectomized rats, whereas [3H]DA did not produce any detectable [3H]E. [3H]CAs in tissues and urine were analyzed by reverse-phase high-performance liquid chromatography. The identities of the [3H]CAs in the urine were further verified by a double-labeling radioenzymatic technique. The results demonstrated that in the rat E can by synthesized outside the adrenals and that DASO4 can serve as an intermediate in such a synthesis. [3H]DASO4 was also converted to [3H]DA and [3H]NE, indicating that it can be metabolized in vivo and could be the source of free DA in urine.

Adrenal Glands↗

Treatment of refractory hypertension with minoxidil.

Twenty patients with hypertension refractory to conventional therapy were treated with minoxidil in combination with a diuretic and a beta-blocker. The mean supine initial blood pressure was 207/128 mm Hg, and the end-treatment pressure was 155/89 mm Hg. Five of the 7 patients with essential hypertension were adequately controlled, as were 8 of the 9 patients with renal failure and all 4 patients with renovascular hypertension. Thus, the overall controll rate was 85%. The duration of treatment ranged from 1 to 30 months, and the minoxidil dosage ranged from 5 to 60 mg/dry electrocardiographic changes characterized by T-wave inversion after starting minoxidil. These changes were reversible in 4 patients. Minoxidil was found to be an effective antihypertensive drug in these patients with refractory hypertension.

Adult↗

Conjugation of catecholamines, a variable to be accounted for in human hypertension.

A subgroup of essential hypertensive (EH) patients with high sympathetic tone had low plasma conjugated norepinephrine (NE) and epinephrine (E), but elevated free NE and E and a hyperresponsiveness to various stimuli to the autonomic nervous system. Pheochromocytoma patients could also be divided according to conjugated NE + E levels, this time into normal and elevated conjugated groups. The latter seem to be somewhat protected by the conjugation, showing less free NE and E 'flooding' during hypertensive crises and lower VMA excretion. The degree of catecholamine conjugation can thus modify the sympathetic tone in hypertension.

Adrenal Gland Neoplasms↗

Effect of captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity.

Seven patients with essential hypertension and seven patients with hypertension associated with renal artery stenosis received captopril (SQ 14225), an inhibitor of angiotensin I converting enzyme. There was a significant reduction in mean blood pressure, from 176/113 +/- 4/3 mm Hg during the control period to 140/90 +/- 5/3 mm Hg during captopril administration. Five patients received captopril alone and nine patients needed hydrochlorothiazide in addition to control their blood pressure. Captopril produced a significant increase in peripheral plasma renin activity. When measured 12 hours after the administration of captopril the angiotensin I converting enzyme activity was found to be similar to that during the control period even though the blood pressure was at or near normal. These findings indicate that although captopril is an effective antihypertensive agent, its action does not depend only on inhibition of plasma angiotensin I converting enzyme activity.

Adult↗

Dopamine-4-O-sulfate: a possible precursor of free norepinephrine.

Incubation of dopamine-4-O-sulfate with purified bovine dopamine-beta-hydroxylase led to the formation of free norepinephrine. The production of free norepinephrine was completely inhibited in the presence of 5.6 mM of fusaric acid, an inhibitor of dopamine-beta-hydroxylase. No sulfatase activity was detected in the incubation medium. The reaction of dopamine-4-O-sulfate with dopamine-beta-hydroxylase followed Michaelis-Menten kinetics, showing an apparent Km of 2.6 mM.

Adrenal Glands↗

Role of the adrenal cortex and sodium in the pathogenesis of human hypertension.

After 30 years of continuous research into the mechanisms of human hypertension, we summarize the results obtained by the members of the multidisciplinary research group on hypertension of the Clinical Research Institute of Montreal on the disturbances of minerlocorticoid activity in a rigorously selected group of patients with early, mild essential hypertension. We attempt to integrate these findings with those of many other groups working on other aspects of hypertensive cardiovascular diseases. On the assumption that the increased peripheral resistance responsible for hypertension results from an imbalance or a disturbance of the equilibrium between the sympathetic nervous system and norepinephrine on one hand, and the vascular tone, sensitivity and responsiveness of the arterial smooth muscle to norepinephrine and to angiotensin II on the other hand, three models that fit the experimental and clinical facts as known at present are described.

Adrenal Cortex↗

Free and conjugated catecholamines in human hypertension.

1. Noradrenaline and adrenaline in the adrenal vein of essential hypertensive patients are almost exclusively (99%) unconjugated or free. However only 17% of dopamine is free, the rest is conjugated. The further the site of sampling from the adrenal vein the closer come the free catecholamines to their normal peripheral venous proportion (noradrenaline + adrenaline 20%, dopamine less than 1% of total catecholamines). Deviations from these patterns help to detect the site and type of secretion of phaeochromocytoma. 2. Essential hypertensive patients have, compared with control subjects, higher conjugated plasma dopamine, less urinary free and conjugated dopamine with blunted urinary free dopamine and sodium responsiveness to frusemide. Conjugated noradrenaline + adrenaline, mean arterial pressure and age are positively interrelated. 3. Patients with primary aldosteronism have elevated plasma and urinary total dopamine. After removal of the adenoma urinary dopamine excretion decreases to normal. 4. Elevated conjugated dopamine appears to reflect a compensatory activation of the dopaminergic vasodilator pathway in hypertension, the total urinary dopamine excretion an intrinsic deficiency or compensatory increase of a dopamine-modulated natriuretic mechanism.

Adrenal Gland Neoplasms↗