Cyclic Nucleotides And PlateLet-Leukocyte Aggregates In Patients With Occlusive Arterial Disease

1981 ◽  
Author(s):  
B Kiersnowska-Rogowska ◽  
M Bielawiec ◽  
F Rogowski ◽  
A Bodzenta ◽  
J Giedrojć

The aim of the work was to study plasma cyclic nucleotides level /cyclic-AMP and cyclic-GMP/ and platelet-leukocyte aggregates in patients with obliterative arteriosclerosis of the lower limbs. The following parameters were investigated: cyclic-AMP and GMP radioimmunochemically by the use of a cyclic-AMP and cyclic-GMP assay kit, platelet leukocyte aggregates by the method of Silbergleit in our modification.The remainder were hospital deaths, five within the first 48 hours, 8 between 2-14 days, and 4 between 14 and 94 days. Five cases showed subendocardial infarction (SI). Four of these occuring out of hospital. The remaining 18 cases were transmural infarctions (TI). Sixteen of 17 hospital deaths exhibited TI.Significant decrease in cyclic-AMP level was found in arteriosclerotic patients in comparison to the control group. No significant changes in cyclic-GMP level were observed. The number of platelet-leukocyte aggregates was significantly higher in these patients.The influence of Hydroxy-ethyl-rutosides /HR/ on investigated parameters was also studie.The significant decrease in the level of cyclic-GMP in plasma was observed in patients after intravenously injection of 1000 mg of HR whereas no changes were found in cyclic-AMP level. The significant decrease in the number of platelet-leukocytes aggregates in the blood obtained after HR injection was also observed.Our results have shown the disturbances of plasma cyclic nucleotides balance and function of platelets and leukocyte in arteriosclerotic patients. This study also suggests that HR may be a modulating agent of these parameters.

1977 ◽  
Author(s):  
M. Bielawiec ◽  
B. Kiersnowska-Rogowska ◽  
H. Łukjan

The diagnostic value and the effect of the therapy on the number and kind of platelet-leukocyte aggregates in patients with arteriosclerosis obliterans of the lower limbs were investigated. The modified Silbergleit’s method was used. 8 types of aggregates were found. The mean number of aggregates in 20 healthy subjects was 8.2, in 52 patients suffering from obliterative arteriosclerosis of the lower limbs this number was significantly higher, that is 63.9. In healthy subjects most of the aggregates were type 1 to 4 whereas in the patients types 3 and 5 were most frequently found. 30 patients were treated for 3 weeks with hydroxyethylrutosides /HR/ - orally 600 mg three times daily or intravenously 1000 mg twice a day. A significant decrease of the number of platelet - leukocyte aggregates in the groups of patients receiving HR was found. The type of aggregates after HR was similar to that found in the control group. In 22 patients receiving nicotinic acid derivatives /orally 300 mg three times daily and intramuscularly 300 mg twice a day/ for 3 weeks no significant changes in the parameter investigated was observed. The method of differential counting of platelet-leukocyte aggregates may be of value in early diagnosis of occlusive arterial disease and in evaluation of their therapy.


1979 ◽  
Vol 57 (6) ◽  
pp. 541-546 ◽  
Author(s):  
H. L. Cailla ◽  
H. Sarles ◽  
M. V. Singer

The secretion of cyclic AMP, cyclic GMP, protein, calcium, and bicarbonate in the pancreatic juice of three nonanesthetized dogs with chronic gastric and duodenal Thomas cannulae has been studied. Intravenous infusions of increasing doses of cholecystokinin–pancreozymin (CCK) (1.5, 3, 6, 12, 24 Crick Harper-Raper (CHR) U kg−1 h−1) were administered together with a continuous submaximal dose of secretin (1 clinical unit (CU) kg−1 h−1). Doubling CCK doses every 45 min induced a parallel increase in the output of both cyclic nucleotides. Cyclic AMP output peaked at between 15 and 30 min for 3 and 6 U kg−1 h−1 of CCK and later for 12 and 24 U kg−1 h−1 of CCK whereas cyclic GMP output increased more constantly. Calcium output followed a pattern similar to that of cyclic GMP secretion. Flow rate and protein output attained their peaks at between 30 and 45 min. A strong linear correlation was found between the quantities of cyclic AMP, cyclic GMP, and the quantities of protein secreted in response to each CCK dose. This study demonstrates the presence of cyclic GMP in the canine pancreatic juice and the dose-dependent stimulation of the secretion of cyclic GMP and cyclic AMP by CCK in the presence of secretin.


1975 ◽  
Author(s):  
O. Ponari ◽  
E. Civardi ◽  
R. Potì ◽  
A. G. Dettori

The responsiveness of fibrinolytic activity and of plasma Factor VIII level to both venous occlusion (v.o.) and i.v. nicotinic acid (N. A.) was investigated in a group of patients with occlusive arterial disease.A marked hyperfibrinolysis, with average decrease of ELT of -55%, was seen after v.o. in such patients, with a rise of F. VIII (average value +30%). A control group of comparable age but with no signs of atherosclerosis, showed similar changes after v.o. (ELT about —65% and F. VIII +60%). A comparable hyperfibrinolytic response was also found in a group of young ( < 40 y.) normal subjects.I.V. administration of N. A. (100 mg) obtained variations of ELT of similar magnitude (—50%) in both groups (patients and age-matched controls). Changes in F. VIII were absent or only moderate.The responsiveness to v.o. in single cases showed no correlation with an index derived from main risk factors (both clinical and biochemical) for thrombosis.Our results do not agree with the hypotesis that an altered responsiveness of vascular fibrinolytic system is an important factor in the pathogenesis of occlusive arterial disease.


Author(s):  
John W. Phillis

SUMMARY:On the basis of the information presented in this review, it is difficult to reach any firm decision regarding the role of cyclic AMP (or cyclic GMP) in synaptic transmission in the brain. While it is clear that cyclic nucleotide levels can be altered by the exposure of neural tissues to various neurotransmitters, it would be premature to claim that these nucleotides are, or are not, essential to the transmission process in the pre- or postsynaptic components of the synapse. In future experiments with cyclic AMP it will be necessary to consider more critically whether the extracellularly applied nucleotide merely provides a source of adenosine and is thus activating an extracellularly located adenosine receptor, or whether it is actually reaching the hypothetical sites at which it might act as a second messenger. The application of cyclic AMP by intracellular injection techniques should minimize this particular problem, although possibly at the expense of new difficulties. Prior blockade of the adenosine receptor with agents such as theophylline or adenine xylofuranoside may also assist in the categorization of responses to extracellularly applied cyclic AMP as being a result either of activation of the adenosine receptor or of some other mechanism. Ultimately, the development of highly specific inhibitors for adenylate cyclase should provide a firm basis from which to draw conclusions about the role of cyclic AMP in synaptic transmission. Similar considerations apply to the actions of cyclic GMP and the role of its synthesizing enzyme, guanylale cyclase.The use of phosphodiesterase inhibitors in studies on cyclic nucleotides must also be approached with caution. The diverse actions of many of these compounds, which include calcium mobilization and block of adenosine uptake, could account for many of the results that have been reported in the literature.


1973 ◽  
Vol 138 (2) ◽  
pp. 381-393 ◽  
Author(s):  
Terry B. Strom ◽  
Charles B. Carpenter ◽  
Marvin R. Garovoy ◽  
K. Frank Austen ◽  
John P. Merrill ◽  
...  

The capacity of allosensitized thymus-derived lymphocytes to destroy target cells bearing donor alloantigens is modulated by the cellular levels of cyclic AMP and cyclic GMP. Increases in the cyclic AMP levels of attacking lymphocytes by stimulation with prostaglandin E1, isoproterenol, and cholera toxin inhibit lymphocyte-mediated cytotoxicity; whereas, depletion of cyclic AMP with imidazole enhances cytotoxicity. The augmentation of cytotoxicity produced by cholinergic stimulation with carbamylcholine is not associated with alterations in cyclic AMP levels and is duplicated by 8-bromo-cyclic GMP. The effects of activators of adenylate cyclase, cholinomimetic agents, and 8-bromocyclic GMP are upon the attacking and not the target cells and occur at the time of initial interaction of attacking and target cells. Indeed, the level of cyclic nucleotide (cyclic AMP and cyclic GMP) at the time of initial cell-to-cell interaction determines the extent of cytotoxicity.


1975 ◽  
Vol 152 (3) ◽  
pp. 583-592 ◽  
Author(s):  
J Mowbray ◽  
J A Davies ◽  
D J Bates ◽  
C J Jones

Perfused rat heart incorporated L-[14C]tyrosine into protein at a constant rate for up to 75 min. A purified bovine growth-hormone preparation (1 mug/ml) stimulated the incorporation to a new constant rate that was more than three times the control rate by 10 min after hormone addition to perfusate. The hormone, however, did not alter the intracellular tracer amino acid pool, and the relationship of this to the aminoacyl-tRNA precursor pool is discussed. It is concluded that the increased incorporation largely reflected a rapid increase in protein synthesis at the ribosomes. Measurements of cyclic nucleotide contents during the perfusion showed that these appeared to vary in a systematic way during the perfusion. This strands in contrast with the constant values given by several other parameters measured in this preparation. Futher, the cyclic nucleotide variation seems to be independent of external effectors. The steady-state performance of the heart correlates more closely the [cyclic AMP]/[cyclic GMP] ratio than with the content of the individual cyclic nucleotides. At 10 min after the addition of growth hormone a slight decrese in cyclic AMP content and a large decrease in cyclic GMP were found, suggesting that the hormone's effect in stimulating protein synthesis may be mediated by a decrease in cyclic nucleotide concentrations or an increase in the [cyclic AMP]/[cyclic |p] ratio. The findings are also consistent with an intracellularly directed role for these nucleotides, and the possibility that the cyclic nucleotide changes are an indirect result of growth-hormone action is discussed.


1998 ◽  
Vol 76 (6) ◽  
pp. 605-612 ◽  
Author(s):  
Karen L Naim ◽  
Prem Rabindranauth ◽  
Harvey R Weiss ◽  
James Tse ◽  
Richard J Leone, Jr. ◽  
...  

The aim of the current study was to determine if lowering myocardial cyclic GMP by guanylate cyclase inhibition would add independently to the positive inotropic effects caused by raising cyclic AMP and if these effects are modified in left ventricular hypertrophy (LVH) produced by aortic valve plication. Isoproterenol (ISO) (0.1 mg·kg-1·min-1) was infused into a branch of the left anterior descending coronary artery of seven control and eight hypertrophy open-chest anesthetized dogs. After 10 min, simultaneous infusion of methylene blue (MB) (2 mg·kg-1·min-1) was initiated at the same site. Hypertrophy increased heart weight and heart weight / body weight ratio. While both drugs increased left ventricular dP/dtmax, no additional global effects were observed in either group. Changes in regional variables followed the same pattern in both groups, i.e., ISO produced an increase that was enhanced by the addition of MB. ISO increased segment shortening, with a significant change in the control group. ISO increased regional force in both groups. The addition of MB increased force above ISO levels, with a significant change in the LVH group. ISO increased regional minute work (g·mm·min-1) (control, 1779 ± 428 to 2541 ± 500; LVH, 1157 ± 253 to 1839 ± 404) and O2 consumption. MB further increased regional work (control, 2993 ± 952; LVH, 2416 ± 853) and O2 consumption. ISO raised cyclic AMP (pmoles·g-1) (control, 468 ± 41 to 580 ± 84; LVH, 445 ± 43 to 562 ± 71) and had no effect on cyclic GMP (pmoles·g-1) (control, baseline 3.27 ± 0.22, ISO 2.87 ± 0.23; LVH, baseline 6.84 ± 1.12, ISO 5.66 ± 0.54). The addition of MB lowered cyclic GMP (control, 2.41 ± 0.26; LVH, 3.68 ± 0.35), but also increased cyclic AMP (control, 1021 ± 121; LVH, 1107 ± 134). Similar results were observed in control hearts using a specific soluble guanylate cyclase inhibitor (ODQ) in terms of changes in local work, O2 consumption, and cyclic nucleotides. Thus, at least part of the positive inotropic response to lowering cyclic GMP was mediated by changes in cyclic AMP in the current model. This was true in both control and LVH animals, although baseline cyclic GMP levels were higher, and a larger reduction in cyclic GMP was observed with MB in the LVH group.Key words: guanylate cyclase, coronary blood flow, myocardial shortening, myocardial work, myocardial O2 consumption, dog.


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