Plasma Cyclic AMP Levels Research Articles

Plasma cyclic adenosine 3',5'-monophosphate (cAMP) levels in hyperthyroid patients.

Plasma cyclic AMP levels were studied in ten subjects with hyperthyroidism before and after propylthiouracilic treatment. In untreated hyperthyroid subjects the plasma cyclic AMP levels were significantly elevated but were normalized when plasma iodothyronine levels declined in the normal range.

Rolipram inhibits leukocyte-endothelial cell interactions in vivo through P- and E-selectin downregulation.

1. Rolipram, a selective phosphodiesterase (PDE) type 4 inhibitor, was used to characterize leukocyte recruitment mechanisms in models of acute and subacute inflammation. Intravital microscopy within the rat mesenteric microcirculation was employed. 2. Mesentery superfusion with PAF (0.1 microM) induced a significant increase in leukocyte rolling flux, adhesion and emigration at 60 min. Rolipram pretreatment, markedly inhibited these parameters by 100, 95 and 95% respectively. 3. Similar effects were observed when the mesentery was superfused with LPS (1 microg ml(-1)) for the same time period and these leukocyte parameters were nearly abrogated by rolipram pretreatment. 4. LPS exposure of the mesentery for 4 h caused a greater increase in leukocyte rolling flux, adhesion and emigration which were inhibited by rolipram administration by 51, 71 and 81% respectively. 5. Immunohistochemistry revealed a significant increase in P-selectin expression after 60 min superfusion with PAF which was attenuated by rolipram. 6. LPS exposure of the mesentery for 4 h caused a significant increase in P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. Rolipram pretreatment down-regulated both P- and E-selectin expression but had no effect on ICAM-1 and VCAM-1 expression. 7. Significant increases in plasma cyclic AMP levels were detected at 4.5 h after rolipram administration. 8. In conclusion, we have demonstrated that rolipram is a potent in vivo inhibitor of leukocyte-endothelial cell interactions. The effects observed are mediated through endothelial P- and E-selectin downregulation. Therefore, selective PDE-4 inhibitors may be useful in the control of different inflammatory disorders.

Heart rate and plasma cyclic AMP responses to isoproterenol infusion and effect of beta-adrenergic blockade in patients with postural orthostatic tachycardia syndrome.

To clarify the pathophysiological mechanism of postural orthostatic tachycardia syndrome (POTS). the responses of heart rate and the plasma cyclic AMP (cAMP) level to isoproterenol infusion in the supine position were evaluated in 10 POTS patients and 10 age-matched controls. Also, the effect of beta-adrenergic blockade on POTS was assessed using the headup tilt test. The POTS patients consisted of two men and eight women, with a mean age of 19.7 years (range. 15-28 years). An exaggerated increase of both heart rate and the plasma cAMP concentration after isoproterenol infusion at a low dose (1 microg/min) was observed in the POTS patients, but not in control subjects. Seven POTS patients received oral beta-blocker therapy. In five of these, symptoms were abolished and there was a smaller heart rate increase during the head-up tilt test. These data suggest that POTS may be more prevalent in young women and that beta-adrenergic hypersensitivity may play a role in the mechanisms of this syndrome. However, a larger series of patients need to be studied in the future.

Endoscopic Biliary Drainage —The Effectiveness of Biliary Drainage in Consideration of the Hepatic Functional Reserve—

Abstract: The present study was designed to determine whether it is possible to estimate the effectiveness of biliary decompression, the duration of functioning patency of the prosthesis and the prognosis after drainage using the hepatic functional reserve (HFR) as an index, in patients with malignant obstructive jaundice in which endoscopic biliary drainage (EBD) or percutaneous transhepatic biliary drainage (PTBD) is performed. Evaluation of HFR was based on the plasma cyclic AMP level at 10 min. in the glucagon test (cyclic AMP10). Furthermore, with respect to HFR, the effectiveness of biliary decompression by EBD was compared with that by PTBD. The criteria of bilirubin decreasing rate “b”, proposed by Shimizu et al. to determine the effectiveness of biliary decompression by PTBD were revaluated in comparison to that of EBD. The following results were obtained. 1 Cyclic AMP10 was useful to estimate the effectiveness of biliary decompression by EBD and PTBD. 2 No relationship was found between cyclic AMP10 and the duration of functioning patency of the prosthesis, which led to the inference that patency may be dependent on various factors in addition to HFR. 3 In terms of the reaction of cyclic AMP10, the prognosis was worse in the poor reaction group than in the good reaction group. It was considered that the reaction of cyclic AMP10 is useful to estimate prognosis. 4 The effectiveness of biliary decompression by EBD was better than that of PTBD in patients with nearly equal cyclic AMP10. 5 In evaluating the effectiveness of biliary, decompression by EBD, it seems to be necessary to modify the standard set points of the criteria of bilirubin decreasing rate “b”, proposed by Shimizu et al. and used with PTBD.

Plethysmographic Evaluation of the Vascular Effects of Human Calcitonin Gene-Related Peptide in Man

Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardiovascular effects that include positive inotropic and chronotropic actions systemic vasodilation, and hypotension in animals and in man. The mechanism of action of CGRP is still, however, not clear, and in particular it is not known whether vasodilation by CGRP occurs by changes in cutaneous or in muscular blood flow, or both. The aim of the study was, therefore, to evaluate the cutaneous and muscular blood flow, at rest and after ischemic test, induced by an IV bolus 25 micrograms human CGRP infusion in 5 healthy normotensive volunteers, using a strain gauge plethysmographic procedure with venous occlusion. Human CGRP provoked a transient but significant decrease in systolic and diastolic blood pressure, associated with tachycardia, marked flushing, a significant increase in plasma noradrenaline, adrenaline, and cyclic AMP levels, and a slight, but significant, decrease in serum total calcium. Moreover, a significant increase in the carpal cutaneous blood flow at rest was observed, with no significant change in the lower extremity muscular blood flow at rest and after ischemic test. Finally human CGRP produced a significant increase in the venous partial O2 pressure and in the hematocrit and a significant decrease in the venous partial CO2 pressure. The results of the present study confirm the acute cardiovascular and metabolic effects of CGRP. In fact, hypotension, tachycardia, flushing, and the increased cutaneous blood flow indicate a systemic vasodilation by the neuropeptide, with a secondary sympathetic response, as documented by the augmented catecholamine and cyclic AMP plasma levels.

Calcium Metabolic Indices, Vascular Retinopathy, and Plasma Renin Activity in Essential Hypertension

The interplays between calcium metabolic indices, retinal vascular status, plasma renin activity and blood pressure were examined in 67 patients with untreated essential hypertension. There was an inverse relationship between plasma ionized calcium and blood pressure (P = .002), whereas albumin-modified total serum calcium was directly related to blood pressure (P = .02). The plasma cyclic AMP level (P = .05) and the 24 h urinary excretion of cyclic AMP (P = .03) were also positively associated with blood pressure. Patients with vascular retinopathy had lower plasma ionized calcium concentrations (P = .01) and higher 24 h urinary cyclic AMP excretions (P = .05) than those without such changes, even when the differences in blood pressure, age, sex and body mass index were taken into account in analyses of covariance. Plasma renin activity did not interfere with the relationships between calcium metabolic indices and blood pressure, nor were there any associations between the renin status and the calcium metabolic indices. These findings suggest that a low concentration of plasma ionized calcium is an independent risk factor for vascular disease.

Inter-relationship between serum potassium and plasma catecholamines and 3′:5′ cyclic monophosphate in alcohol withdrawal

Serial analyses of serum potassium and plasma epinephrine, norepinephrine and adenosine 3′:5′-cyclic monophosphate (cyclic AMP) concentrations were measured in 13 patients with alcohol withdrawal, six of whom presented delirium tremens. Patients with delirium showed at admission levels of potassium (3.45 ± 0.45 mmol/l) lower ( P < 0.02) than patients without delirium (3.81 ± 0.14 mmol/l). Three patients were hypokalemic, all of them with delirium. Serum potassium increased significantly in all the patients during evolution. A close negative correlation ( r = − 0.751) between the intensity of withdrawal and serum potassium was observed. Plasma epinephrine concentrations were increased at admission (623 ± 192 pmol/l), patients with delirium showing greater values (705 ± 137 pmol/l). As the alcohol withdrawal improved, plasma epinephrine concentration decreased. Plasma norepinephrine concentrations were also increased at admission (3422 ± 1451pmol/l), but did not change significantly during evolution, being similar in patients with and without delirium. Plasma cyclic AMP levels were high at admission (40.4 ± 24.3 nmol/l) and increased significantly ( P < 0.05) during evolution. The data obtained suggest that in patients with alcohol withdrawal, as symptomatology improves, plasma epinephrine decreases, while plasma norepinephrine remains increased. The combined actions of the two facts — less β-stimulus, maintaining of α-stimulus — would comprise a significant increase of kalemia, that in cases of initial hypokalemia would lead to normal values of serum potassium.

Assessment of autonomic nervous function in patients with vibration syndrome using heart rate variation and plasma cyclic nucleotides.

A case-control study was performed to investigate the autonomic nervous function in vibration syndrome. The subjects were 20 patients with a history of Raynaud's phenomenon (vibration white finger (VWF) (+) group), 20 patients without such a history (VWF(-) group), and 20 healthy workers (control group). Their ages and years under medical treatment for vibration syndrome were matched individually among the groups. They were examined using the test of R-R interval variations in the electrocardiogram at rest and during deep breathing and the test of plasma cyclic nucleotide (cyclic AMP and cyclic GMP) responses to whole body exposure to cold. The heart rate variation resulting from respiratory arrhythmia reflects parasympathetic activity; the changes of plasma cyclic AMP and GMP levels reflect sympathetic and parasympathetic receptor functions. The reduced R-R interval variations were observed in the VWF(+) group. Although exposure to cold induced a significant increase of plasma cyclic AMP level, the percentage increase was almost the same among the three groups. The response of plasma cyclic GMP level to cold exposure was highly activated in the VWF(+) and the VWF(-) groups. On the basis of these results, it is considered that the parasympathetic function of patients with vibration syndrome is lower at rest, and that exposure to cold induces a hypperresponse of the parasympathetic nervous system and the alpha-2 adrenergic mechanism as a result of activation of the sympathetic nervous system. Moreover, in patients with VWF, the contribution of the alpha-2 adrenergic mechanism is presumably larger than that in the patients without VWF.

Plasma cyclic nucleotide levels in patients with refractory anaemia with excess of blasts

To verify the clinical usefulness of extracellular cyclic nucleotide determinations as tumour markers in preneoplastic syndromes, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were monitored in 47 patients with refractory anaemia with excess of blasts (35 RAEB and 12 RAEBt), 20 of whom progressed to acute leukaemia during the observation period. The control group consisted of 45 healthy subjects matched for age and sex. In all groups of patients plasma cAMP levels were within the normal range, whereas plasma cGMP levels were significantly higher than those of normal subjects in both RAEB and RAEBt patients, and increased further when progression to acute leukaemia occurred. These data suggest that serial determinations of plasma cGMP may be useful to monitor the progression of the disease, though there is no evidence that cGMP values at diagnosis may have a prognostic significance.

Plasma cyclic AMP in non-abstinent chronic alcoholics. Relation to clinical parameters

Plasma cyclic AMP levels were determined in a group of 36 male chronic alcoholics during a period of their usual alcohol intake and compared to 29 normal controls. Significantly lower values ( P < 0.005) were found in the patient group. The possible influence of age, chronicity of drinking, family history of alocholism, dementia and liver injury on plasma cAMP levels was examined by multiple regression analysis. No influence of those factors could be established except that demented alcoholics showed a trend toward higher levels than a non-demented subgroup. The role of reduced β-adrenergic receptor activity during chronic alcohol ingestion is discussed in relation to the above findings.

The reduction of renin and aldosterone as a response to acute hypervolemia is blocked by a monoclonal antibody directed against atrial natriuretic peptides

We have previously reported that the strong diuresis, natriuresis and urinary cyclic GMP excretion after acute volume loading in rats are caused by ANP and can be blocked by additionally given monoclonal antibodies directed against ANP. The present report describes that in contrast to the changes in ANP and cyclic GMP, the plasma renin activity and aldosterone concentration are decreased after volume loading. This decrease is completely blocked by simultaneous administration of the monoclonal antibodies. Plasma cyclic AMP levels are not affected. From this study it seems to be clear that the inhibition of the renin-aldosterone system is not direct effect of volume expansion but is specially mediated by the released ANP.

Adrenomedullary and β-adrenergic participation in enhanced sympathetic pressor responses of spontaneously hypertensive rats

The β-adrenergic and adrenomedullary components of pressor to sympathetic nerve stimulation were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The effects of electrical stimulation of the entire spinal cord of pithed rats pretreated with tubocurarine and atropine were studied on systolic bloob pressure, heart rate and plasma cyclic AMP levels. The heart rate increase upon low frequency stimulation (1 Hz) and blood pressure elevation upon stimulation at higher frequencies (3 and 5 Hz) were higher in SHR than in WKY whereas the increase in circulating cyclic AMP level was not different in the two strains. Pretreatment with propranol (2.5 mg·kg −1) further enhanced the pressor responses in SHR but not in WKY, although it inhibited the heart rate acceleration and decreased the circulating level of cyclic AMP similarly in the two strains. After acute adrenalectomy, the elevations of blood pressure and circulating cyclic AMP levels were reduced to an identical level in SHR and WKY. These results show that the marked enhancement of the pressor response observed in SHR upon stimulation of the entire sympathetic outflow is most of adrenomedullary origin and includes a hypotensive component due to β-adrenoceptor stimulation which is not present in WKY.

Plasma cyclic nucleotide levels in acute leukemia patients

To verify the clinical usefulness of extracellular cyclic nucleotide determination as a tumor marker, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in 70 normal subjects and 173 acute leukemia patients studied in different stages of their disease. Mean plasma cAMP levels were similar in leukemic and normal subjects, although in 48 patients in the active stage of the disease, first diagnosis, or relapse, the cAMP values were below the normal range, and most of these patients failed to respond to chemotherapy. Plasma cGMP levels were markedly elevated in untreated patients, normalized in all patients who attained complete remission, and increased promptly to pretreatment values in patients who relapsed, suggesting that their determination may be useful to monitor the patients' response to treatment.

Plasma Cyclic Nucleotide Levels in Acute Leukemia Patients

Abstract To verify the clinical usefulness of extracellular cyclic nucleotide determination as a tumor marker, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in 70 normal subjects and 173 acute leukemia patients studied in different stages of their disease. Mean plasma cAMP levels were similar in leukemic and normal subjects, although in 48 patients in the active stage of the disease, first diagnosis, or relapse, the cAMP values were below the normal range, and most of these patients failed to respond to chemotherapy. Plasma cGMP levels were markedly elevated in untreated patients, normalized in all patients who attained complete remission, and increased promptly to pretreatment values in patients who relapsed, suggesting that their determination may be useful to monitor the patients' response to treatment.

Plasma cyclic AMP and GMP levels in essential hypertension: interrelationship among plasma cyclic nucleotides sympathetic activity and renin-angiotensin system

Plasma cyclic AMP and GMP levels in essential hypertension: interrelationship among plasma cyclic nucleotides sympathetic activity and renin-angiotensin system

High doses of fluoride do not affect cyclic AMP levels in human and rat plasma or urine.

The effect of fluoride ingestion on plasma and urinary cyclic AMP levels was studied in healthy volunteers, children undergoing prophylactic fluoride treatment and in rats. In the first series of experiments fluoride ingestion led to a 20-fold increase in plasma fluoride concentration, which was unrelated to changes in plasma cyclic AMP. The only significant effect on plasma cyclic AMP occurred prior to fluoride, an effect attributed to stress. In the second series performed in children increases in urinary F- of up to 200-fold were associated with slight but nonsignificant changes in cyclic AMP excretion. In rat experiments the blood sampling procedure was associated with a rise in plasma cyclic AMP. When this was prevented by pretreatment with propranolol (3 mg/kg), the effect of fluoride (50 ppm in the drinking water) was tested. A fall in urine production was not associated with any change in cyclic AMP excretion or in nephrogenic cyclic AMP. It is concluded that if fluoride alters cyclic AMP in rats and man the effect is small and easily masked by other factors such as catecholamine release following stress.

Rapid increase in plasma and urinary cyclic GMP after bolus injection of atrial natriuretic factor in man.

We studied the effects of a bolus injection of 50/micrograms synthetic human atrial natriuretic factor (ANF) on the cyclic GMP and cyclic AMP levels in plasma and urine of eight normal men. Administration of the hormone increased basal immunoreactive (IR-) ANF levels in plasma 2.8-fold to 110 pM three minutes after injection. Thereafter, IR-ANF levels rapidly declined to basal levels. Plasma cyclic GMP levels increased 2.6-fold to 16.6 nM within 6 minutes after ANF and decreased to near basal values within 30 minutes. Urinary cyclic GMP excretion increased 2.8-fold, whereas urinary volume and sodium excretion increased less than two-fold in the 30 minutes after ANF. Plasma cyclic AMP levels did not change. The data indicate that changes in plasma IR-ANF levels are followed by changes in plasma cyclic GMP and in urinary cyclic GMP excretion and suggest that cyclic GMP is a biological marker for circulating ANF in man.

Prostaglandin E2 and cyclic nucleotides in plasma and urine of colonic cancer patients

Prostaglandin E2 and cyclic nucleotide levels were measured in plasma and urine of 14 patients with colonic cancer. The measurements were performed 1 day before and 8 days after the removal of the tumor by operation. There was no difference between the plasma PGE2 levels (in form of the 13, 14-dihydro-15-keto metabolite) before and after the operation, but they were significantly higher than the level of a control group. No differences before and after operation were found between plasma cyclic AMP (cAMP) levels, plasma cyclic GMP (cGMP) levels, urinary cAMP levels and urinary cGMP levels. All the cyclic nucleotide concentrations were within the normal range. No correlation could be found between the stage of the tumor spread and any of the substances analyzed. The conclusions are that plasma PGE2 and plasma and urinary cyclic nucleotides do not originate from the colonic tumor tissue, and that these substances cannot be used as tumor markers.

Plasma glucagon and catecholamines during exhaustive short-term exercise.

Plasma glucagon and catecholamine levels were measured in male athletes before and after exhaustive 15 min continuous running and strenuous intermittent short-term exercise (3 X 300 m). Blood lactate levels were higher after the intermittent exercise (mean 16.7 mmol X 1(-1)) than after the continuous running (mean 7.1 mmol X 1(-1)). Plasma glucagon concentration increased during continuous running and intermittent exercise by 41% and 55%, respectively, and the increases in plasma noradrenaline concentration were 7.7- and 9.1-fold compared with the respective pre-exercise values. Immediately after the exercises plasma cyclic AMP, blood glucose and alanine levels were elevated significantly. The data suggest that the sympathoadrenal system is of major importance for liver glucose production during high-intensity exercises. Catecholamines directly stimulate liver glucose production and may indirectly stimulate it by enhancing the secretion of glucagon.

Increased release of cyclic adenosine monophosphate into jugular vein in response to isoproterenol administration

Catecholamine administration elevates plasma cyclic AMP (cAMP) levels but the source of the cAMP is unknown. To determine possible sources, plasma cAMP levels were determined in blood vessels across the head, liver, kidney and lung in anesthetized dogs infused with the β-adrenergic agonist, isoproterenol. Only the head showed an increased release of cAMP into the blood. The kidneys removed cAMP from the blood while liver and lung showed no change. This in vivo demonstration of release of cAMP from the head represents contributions from brain and facial muscles and may be a useful approach to study brain involvement in the action of various hormones and drugs.