High levels of circulating prorenin in pregnancy.
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Enzyme Precursors↗
Biomedical subjects
T Lenz
Publications and source records attributed to T Lenz.
Restricted alpha- and beta-adrenoceptor affinity of sulfoconjugated catecholamines in human mononuclear leukocytes, platelets, and fat cells and reduction of the postreceptor mechanisms.
The physiologic significance of the racemic 3-O-sulfate esters of epinephrine (EPI-3-O-S) and norepinephrine (NE-3-O-S) as well as 4-O-sulfoconjugated dopamine (DA-4-O-S) was evaluated. For this purpose these conjugated catecholamines (CA) were synthesized and investigated with respect to their alpha 2- and beta 2-adrenoceptor affinities and their biological activity in three different human cell systems: in mononuclear leukocytes (MNL), platelets, and fat cells. The unequivocal identification and the minimal degree of contamination of the synthesized sulfoconjugates with free CA was proved by 1H-NMR and by high-performance liquid chromatography with amperometric detection (HPLCA) respectively. In isolated human MNL, beta-adrenoceptor affinities of these conjugated CA were determined in competition experiments with the lipophilic nonspecific radioligand (-) 125I-cyanopindolol (ICYP) and, in addition, with the hydrophilic ligand 3H-CGP12177. With both ligands the affinity constants (KD) of the sulfoconjugated CA under investigation were about 100- to 1000-fold higher when compared with the respective free amines. Moreover, these sulfoconjugated CA per se induced no intracellular production of cyclic adenosine monophosphate (cAMP) in MNL. In comparison with the free amines, metanephrine (MN) and normetanephrine (NMN) showed a highly reduced competitive potency on the MNL beta-adrenoceptors labelled with 3H-CGP or ICYP. The KD values for MN and NMN in competition studies with ICYP were 10- and 5-fold higher than in those with 3H-CGP respectively, indicating a restricted access of MN and NMN to intracellular receptors. The adenylate cyclase system was not stimulated at all by MN or by NMN. In human platelets EPI-3-O-S and NE-3-O-S neither competed with the specific alpha 2-adrenoceptor antagonist 3H-yohimbine nor elicited any aggregation response at all. MN and NMN exhibited an about 40-fold reduced affinity for alpha 2-adrenoceptors in platelets when compared with the respective free amines and elicited no aggregation response at all. However, in the presence of MN and NMN the EPI- and NE-induced platelet aggregation was dose-dependently attenuated. These findings reveal an alpha 2-adrenoceptor antagonistic potency of MN and NMN. In human adipocytes EPI-3-O-S and NE-3-O-S were 100- to 1000-fold less potent to inhibit lipid mobilization via alpha 2-adrenoceptors as well as to stimulate the beta-adrenoceptor mediated lipolysis when compared with free CA.
Adipose Tissue↗
Influence of exercise in water on hormonal, metabolic and adrenergic receptor changes in man.
We investigated hormonal, metabolic, and cardiovascular adaptations as well as changes of alpha 2- and beta 2-adrenergic receptors in response to three different exercise performances in water: 1000 m fin swimming with or without a neoprene suit and, additionally, 600 m diving with a breathing apparatus while performing several tasks. Eight male divers participated in the study. Blood samples were taken at rest on land, 10 min after water immersion, immediately after exercise, and after 20 min recovery. Both free and sulfoconjugated norepinephrine (NE) increased exercise-dependently. Moreover, heat loss in water caused elevation of plasma free NE. Free epinephrine (EPI) increases showed a highly significant correlation with NE except during fin swimming with a neoprene suit where EPI concentrations were constantly higher. ACTH and cortisol levels rose during exercise and paralleled those of plasma NE. Plasma aldosterone decreased in response to water immersion at rest. Blood volume regulating hormones such as plasma renin, aldosterone, and vasopressin were significantly higher during physical exercise. Moreover, increased pressure conditions during diving caused significantly higher secretion rates of all of these hormones, resulting in a higher systolic blood pressure. This clinical issue might be considered when examining diving ability. Lipolysis was elevated to the same degree after the three exercise schedules had been applied. As expected, plasma glucose also increased during physical activity. The lactate values observed after fin swimming, but not after diving with a breathing apparatus were closely related to NE. The lowest lactate levels were obtained during air-assisted diving.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Sulfoconjugated catecholamines: lack of beta-adrenoceptor binding and adenylate cyclase stimulation in human mononuclear leukocytes.
The racemic 3-O-sulfates of epinephrine and norepinephrine as well as 4-O-sulfoconjugated dopamine were synthesized, highly purified and investigated with respect to their beta-adrenoceptor affinities and relative potencies in the receptor-coupled adenylate cyclase system in isolated human mononuclear leukocytes. The receptor affinities of all catecholamine sulfates were reduced at least 1,000-fold when compared to those of the free catecholamines. Furthermore, catecholamine sulfoconjugates did not produce intracellular cAMP signals. In contrast to the sulfated catecholamine metabolites, the 3-O-methylated catecholamines metanephrine and normetanephrine were found to behave as endogenous beta-adrenoceptor-competing agents with lower beta-receptor affinities than the corresponding free catecholamines. No beta-receptor agonist activity in the adenylate cyclase system was found with metanephrine and normetanephrine. Our data provide direct evidence that sulfoconjugation renders catecholamines inactive as beta-receptor ligands and must thus be regarded as a mechanism to control adrenergic action at the prereceptor level by a buffering of the concentration of free catecholamines. The physiological significance of a potential role of 3-O-methylated catecholamines as endogenous beta-receptor antagonists has to be further clarified.
Adenylyl Cyclases↗
Effects of acute hypermagnesaemia on intracellular calcium concentration and adrenergic activity.
The effects of acute hypermagnesaemia on intracellular free calcium and adrenergic activity were investigated in six normotensive volunteers given intravenous magnesium sulphate for 3 h. The free calcium concentration in platelets decreased after the first hour of infusion (P less than 0.05), but did not remain significantly depressed after 2 and 3 h of continued infusion. Plasma noradrenaline increased during the infusion (P less than 0.05), with no change in plasma adrenaline. The results demonstrate that the effects of intravenous magnesium sulphate on free intracellular calcium and plasma catecholamines are similar to those described with calcium antagonists.
Adult↗
Changes in sensitivity to angiotensin II in platelets.
Our study on intracellular effects of angiotensin II in human platelets showed that: (1) angiotensin II increases intracellular free calcium in platelets via a receptor-operated mechanism and this increase is dose-dependent; (2) the effect on platelet intracellular free calcium depends on the extracellular calcium concentration; (3) ACE inhibition leads to an increased sensitivity of intracellular free calcium to angiotensin II but does not alter epinephrine-induced calcium increase; (4) nifedipine reduces the susceptibility of platelet intracellular free calcium for angiotensin II.
Administration, Oral↗
Platelet intracellular free calcium and hypertension.
Platelet intracellular free calcium concentration was assessed by the quin-2 method in 38 patients with essential hypertension and in 35 normotensive subjects. The concentrations were found to be significantly higher in the hypertensive patients (p less than 0.05); however, there was a wide overlap between the values of both groups. In addition, we determined platelet intracellular free calcium in another model of increased blood pressure, the blood pressure elevation following administration of the synthetic mineralocorticoid fludrocortisone. Administration of 0.8 mg fludrocortisone per day to eight normotensive volunteers resulted in a pronounced increase in intracellular free calcium after the first week and a decrease toward control levels thereafter, while blood pressure remained elevated throughout the period of fludrocortisone administration. Our findings suggest that an increase in intracellular free calcium concentration is a transitory phenomenon and not directly related to the blood pressure elevation.
Adult↗
Platelet intracellular free calcium during dynamic exercise.
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Adult↗
[Effect of somatostatin on hypercalcemia stimulated gastric juice and exocrine pancreas secretion in the human].
Hypercalcemia produced in healthy volunteers by intravenous infusions of calciumgluconolactobionate increased outputs of gastric acid, pepsin, and pancreatic enzymes. Hypercalcemia did not affect gallbladder emptying and serum gastrin values. Further, intravenous somatostatin (SRIF, 5 micrograms/kg.h) markedly inhibited secretion of gastric acid (p less than 0.01), pepsin (p less than 0.05), and pancreatic enzymes (p less than 0.02) stimulated by hypercalcemia. SRIF-inhibited outputs were below basal values. These results indicate that the inhibitory effect of SRIF on exocrine cells of the human gastrointestinal tract can not be reversed by extracellular hypercalcemia.
Adolescent↗
Humoral and blood pressure effects of the angiotensin converting enzyme inhibitor ramipril in essential hypertension.
The humoral and antihypertensive activities of the angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0] octane-3-carboxylic acid (ramipril, Hoe 498) were investigated in 10 patients with essential hypertension (WHO stage I or II). After a 7-day placebo period, the patients were treated with 5 mg ramipril orally once daily for 14 days. Peak serum concentrations of the active metabolite M1 (dicarboxylic acid) of 5.4-62.0 ng/ml were observed 2-6 h after the first oral dose. The maximum ACE inhibition of 95% was reached 2-4 h after the first oral dose, inhibition exceeded 70% 24 h after dosing. The maximum drop in the systolic and diastolic blood pressure (random zero sphygmomanometer) was measured 4 h after ramipril (p less than 0.02, p less than 0.01), but blood pressure on days 7 and 14 of the treatment period was not different from pretreatment values. Automatically recorded blood pressure results showed a marked reduction of both systolic and diastolic blood pressure during treatment compared to placebo. No side effects occurred. From the present data it is concluded that ramipril is a potent ACE inhibitor in hypertensive patients and that further controlled studies are required for the evaluation of the antihypertensive effect of 5 mg ramipril in essential hypertension.
Adult↗
Haemodialysis in 'hepatorenal syndrome': report on two cases.
We report two patients with hepatorenal syndrome who recovered from oliguria and renal failure after temporary treatment with haemodialysis. Hepatorenal syndrome developed under diuretic treatment in both patients. Volume expansion, dopamine, and prostaglandin I2 did not improve renal function. In the one patient with alcoholic cirrhosis, renal biopsy showed only minimal alterations of glomeruli, tubuli, and arterial vessels. In the other case, the deterioration and improvement in renal function parallelled changes in acute alcohol-toxic hepatic function. We conclude that haemodialysis should be considered for treatment of hepatorenal syndrome in selected patients where reversal of liver failure can be expected.
Acute Kidney Injury↗
Free intracellular calcium in essential hypertension. Effects of nifedipine and captopril.
The acute effects of nifedipine (20 mg sublingually) and of captopril (12.5 mg orally) on blood pressure and on platelet intracellular free calcium were investigated in 11 and 12 patients, respectively, with essential hypertension. Platelet calcium was measured by the Quin 2 method. Application of both drugs resulted in a significant fall in blood pressure within 60 min. Platelet calcium, however, was lowered by nifedipine only. There was no correlation between blood pressure reduction and changes in platelet calcium. Platelet intracellular free calcium concentration was 99 +/- 3 nmol in 30 normotensive subjects and 109 +/- 5 nmol (+/- s.e.m.) in 26 patients with essential hypertension (P < 0.05). There was a wide overlap between the values of normotensives and hypertensives. Thus there is no positive evidence of an increased platelet intracellular free calcium concentration in a large proportion of patients with essential hypertension.
Adult↗
Intracellular free calcium and ionized plasma calcium during mineralocorticoid-induced blood pressure increase in man.
Intracellular free calcium is considered to play a key role in vascular smooth muscle contraction. Platelet-free intracellular and plasma total and ionized calcium were assessed during mineralocorticoid-induced blood pressure increase in eight normotensive subjects receiving 0.8 mg fludrocortisone per day for 6 weeks. Blood pressure rose within 1 week and showed a further increase up to the 6th week. Plasma noradrenaline and renin activity (PRA) showed a decrease after 1 week and remained suppressed throughout the study. Ionized plasma calcium fell during mineralocorticoid treatment without any significant changes in total plasma calcium. Intracellular free calcium markedly increased after 1 week and decreased towards control levels thereafter. Previous studies have shown that after 1 week of fludrocortisone administration total peripheral resistance is still normal or even subnormal, whereas it is increased after 6 weeks. Therefore, the initial increase in intracellular free calcium, if also present in arteriolar smooth muscle cells, does not appear to be directly related to the final elevation of total peripheral resistance.
Adolescent↗
[Athrombocytosis during cefotaxim-azlocillin combination therapy].
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Azlocillin↗
Yersinia enterocolitica septicemia during long-term immunosuppressive treatment.
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Humans↗
Tachyarrhythmia in yersinia arthritis.
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Adult↗
Effect of nifedipine and verapamil on alpha-receptor-activation in patients with essential hypertension.
The question of whether the hypotensive effect of calcium entry blockers involves an interaction with alpha-adrenergic receptors was examined. The effect of nifedipine subl. (20 mg, n = 9) and of verapamil p.o. (160 mg, n = 9) on the pressor effect of the unselective alpha-adrenergic agonist noradrenaline, as well as on 3H-yohimbine binding to platelet alpha 2-adrenoceptors was studied in patients with essential hypertension. In addition, the effect of nifedipine on reactivity to the selective alpha 1-adrenergic agonist phenylephrine was investigated (n = 9). Nifedipine caused a significant reduction of reactivity to noradrenaline (P less than 0.01), along with a significant decrease in binding sites (P less than 0.01). Affinity to the alpha 2-receptors was unchanged. Verapamil, although equally effective in lowering blood pressure, had no effect on the pressor response or binding sites. The pressor effect of the alpha 1-agonist phenylephrine was reduced (P less than 0.01) by nifedipine. Nifedipine may therefore affect both alpha 1- and alpha 2-adrenoceptors in patients with essential hypertension. Since verapamil did not affect the pressor response to noradrenaline or yohimbine-binding, the interaction with alpha 2-adrenoceptors does not appear to be a general prerequisite for the hypotensive action of calcium entry blockers.
Adult↗
Strain characteristics and features of ocular infection of herpes simplex virus type 1 isolates.
Herpes simplex virus type 1 isolates from 63 patients with herpetic keratoconjunctivitis were investigated. For the purpose of detecting strain differences neurovirulence was determined in mice, and viral DNA's were analyzed by digestion with EcoRI and Hind III restriction endonucleases. Neurovirulence differed by a factor up to 10(5) between individual strains and proved to be independent of the ratio between infectious and noninfectious particles in the stocks used. The endonuclease cleavage patterns revealed differences of the viral DNA structure which permitted us to distinguish seven clusters of strains. Correlations between neurovirulence and DNA markers could not be established nor could correlations be found between these markers and features of disease. The main reason for not finding a relationship in the latter case may be attributed to the significant role of host factors in the course of herpetic diseases.
Adolescent↗