Plasma level of norepinephrine, cyclic AMP and cyclic GMP in essential hypertension.
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Biomedical subjects
Publications and source records attributed to M Ban.
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Peripheral blood lymphocytes from 31 normal subjects and 29 patients with heart diseases were stimulated by isoproterenol, and cyclic AMP level in lymphocytes was assayed. Simultaneously plasma norepinephrine concentration at rest was measured. In normal subjects the generation of cyclic AMP after the stimulation decreased with age. The response of lymphocytes in patients of NYHA classes III and IV was significantly smaller than in the normal, age-matched control. Plasma norepinephrine concentration of patients of classes II, III, and IV rose significantly above normal. In congestive heart failure, a significant correlation between plasma norepinephrine concentration and increase of lymphocyte cyclic AMP was demonstrated. From these results it was suggested that beta-adrenergic receptors in congestive heart failure were desensitized.
The plasma concentrations of norepinephrine (NE), adenosine cyclic 3', 5'-monophosphate (cyclic AMP), and guanosine cyclic 3', 5'-monophosphate (cyclic GMP) were measured serially for 2 weeks after the onset of symptoms in 17 patients with acute myocardial infarction (AMI). The mean concentrations of NE in patients without complications were significantly elevated during the first 2 days following AMI. There was a significant correlation between the maximum concentration of plasma NE and of plasma CK. The mean concentrations of plasma cyclic AMP and cyclic GMP in patients without complications were significantly elevated on the first day and for 8 days respectively following AMI. The concentration of plasma cyclic AMP on admission in patients with complications was significantly higher than that in those without complications. There were significant correlations between the maximum concentration of plasma cyclic AMP and those of plasma CK, GOT, and LDH. Significant but weak correlations between the concentration of plasma NE and those of cyclic AMP and cyclic GMP were found. The results of the present study suggest an enhanced sympathetic nervous system activity at an early stage of AMI, a prolonged enhancement of parasympathetic nervous system activity in the course of AMI, and the potential value of plasma cyclic AMP concentrations as a useful index to estimate the seriousness and size of AMI.
To evaluate the sympathetic nervous activity in chronic hypoxic states, the plasma concentrations of norepinephrine (NE), cyclic adenosine 3', 5'-monophosphate (cyclic AMP), cyclic guanosine 3', 5'-monophosphate (cyclic GMP) and dopamine-beta-hydroxylase (DBH) enzyme activity were measured in 32 patients with pulmonary tuberculosis and 30 normal volunteers. Moreover, the peripheral arterial-venous difference of concentration of these substance, arterial blood gas levels and spirometric data were studied in these patients. The results of this study demonstrated that the plasma NE and cyclic AMP concentrations were directly related to the degree of hypoxemia and some of the spirometric parameters in these patients. It is concluded that sympathetic nervous activity was augmented in chronic hypoxic states, especially with chronic respiratory failure.
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To evaluate the activity of the sympathetic nervous system in chronic renal failure, plasma norepinephrine (NE) and dopamine-beta-hydroxylase (DBH) activity were measured by a radioenzymatic assay and a photometric assay respectively. The level of plasma NE was significantly higher in 14 patients with hemodialysis than in healthy individuals (p less than 0.001). The level of plasma NE fell significantly in 6 patients with hemodialysis receiving 0.30-0.45 mg/day of clonidine hydrochloride (a depressor of the sympathetic outflow from the central nervous system) (p less than 0.05). Systolic blood pressure was correlated with the level of plasma NE in patients with hemodialysis who were not receiving clonidine. They had high level of plasma NE and low level of plasma DBH activity. Therefore, this findings suggest that high level of plasma NE in chronic renal failure is caused not only by decreased urinary excretion, but also by increased overflow from the sympathetic nervous clefts.
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Effects of exogenous PG E1 on the level of human plasma norepinephrine (NE), dopamine-beta-hydroxylase (DBH) activity, cAMP, cGMP, free fatty acids (FFA) as well as pulse rate and blood pressure were studied. Significant decreases of blood pressure and increases of pulse rate were observed after 20 min of the infusion of 0.05 microgram/kg/min of PG E1. The level of plasma NE increased by 174% (p less than 0.005) after the infusion. However, the increase of DBH activity was not significant. There was a tendency of increase of plasma level of FFA. These results suggested that the infusion of PG E1 caused an augmented sympathetic nervous activity due to systemic hypotension induced by PG E1.
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Bicuculline and 3 chemical derivatives were assayed on a variety of biological systems. Consistent with reports of studies on other animals, some of these compounds caused convulsions in insects and blocked inhibitory postsynaptic potentials in insect muscle. They all potently inhibited mouse brain acetylcholinesterase. Bicuculline and its analogs inhibited the binding of GABA in vitro to sites in crayfish muscle membranes which have properties of receptor sites; this site of action could explain the activity of bicuculline at arthropod neuromuscular junctions. These compounds, at high concentrations (over 100 muM), also inhibited GABA uptake by mouse brain homogenates at 0 degrees C apparently non-competitively. Bicucine methyl ester inhibited GABA transport by brain at 37 degrees C, consistent with non-specific membrane effects at high concentrations of drug. These and other observations cast doubt upon the specificity of bicuculline-like compounds for action on GABA synapses, especially for in vitro studies at high drug concentrations (over 10 muM). The neuroactivity of low doses of bicuculline is apparently not explained by these in vitro effects, and could very well be due to inhibition of GABA synapses at either receptor or ionophore sites. At physiological conditions of pH and temperature, bicuculline is hydrolyzed at its lactone moiety to the less active compound bicucine; this could lead to underestimates of the biological activity of bicuculline. More stable analogs studied so far are not more potent, however.
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