Summary
In rabbits receiving an atherogenic diet for 2 months, the ATP content of platelet rich plasma (PRP) and arterial tissue was significantly elevated as compared to normal rabbits. This increase in ATP levels of platelets from atherosclerotic rabbits was paralleled by higher basal as well as PGI2-induced cAMP levels. In arterial tissues, an increase was only obtained in PGI2-stimulated cAMP content.
Treatment with dipyridamole (DPD) for 4 weeks resulted in a reduction of the ATP content in platelets and arterial tissue from atherosclerotic rabbits to values seen in normal animals. Again, the reduction of ATP content was reflected in a decrease of basal as well as PGI2-induced cAMP levels in platelets, whereas in arterial tissue a decrease was only obtained in PGI2-induced cAMP content. At the same time, DPD treatment enhanced atherosclerotic plaque formation in the aortic wall.
The enhanced atherosclerotic plaque formation seen in DPD treated atherosclerotic rabbits may be linked to the inhibition of adenosine uptake, resulting in a decrease of the adenine nucleotide pools of arterial wall cells. The decrease also caused a reduction in PGI2-induced cAMP content. This effect may be linked to altered proliferative activity, since in many cell types, stimulation of cAMP levels results in reduced proliferation rates.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bono, D. P., Gordon, J. L., MacIntyre, D. E., Pearson, J. D.: Active transport of adenine and adenosine by blood platelets and cultured endothelial cells. Br. J. Pharmacol. 58, 466P (1976)
Born, G. V., Mills, D. C. B.: Potentiation of the inhibitory effect of adenosine on platelet aggregation by drugs that prevent its uptake. J. Physiol. (Lond.) 202, 41P (1969)
Breddin, K., Krzywanek, H. J., Bald, M., Kutschera, J.: Is enhanced platelet aggregation a risk factor for thrombo-embolic complications in atherosclerosis? In: Platelet aggregation and drugs (L. Caprino, E. C. Rossi, eds.), pp. 197–203. New York: Academic Press 1974
D'Angelo, V., Mysliwiec, M., Donati, M. B., Gaetano, G.: Defective fibrinolytic and prostacyclin-like activity in human atheromatous plaques. Thrombos. Haemostas. 39, 535–536 (1978)
Dembinska-Kiec, A., Gryglewska, T., Zmuda, A., Gryglewski, R. J.: The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis in rabbits. Prostaglandins 14, 1025–1035 (1977)
Dembinska-Kiec, A., Rücker, W., Schönhöfer, P. S.: PGI2 enhanced cAMP content in bovine coronary arteries in the presence of isobutylmethylxanthine. Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 107–110 (1979a)
Dembinska-Kiec, A., Rücker, W., Schönhöfer, P. S.: Effects of dipyridamole in experimental atherosclerosis: Action of PGI2, platelet aggregation and atherosclerotic plaque formation. Atherosclerosis 33, 315–327 (1979b)
Dieterle, Y., Ody, C., Ehrensberger, A., Stadler, H., Junod, A. F.: Metabolism and uptake of adenosine triphosphate and adenosine by porcine aortic and pulmonary endothelial cells and fibroblasts in culture. Circ. Res. 42, 869–876 (1978)
Gilman, A. G.: Protein binding assay for adenosine 3′:5′-cyclic monophosphate. Proc. Natl. Acad. Sci. USA 67, 305–312 (1970)
Gryglewski, J. R., Dembinska-Kiec, A., Chytkowski, A., Gryglewska, T.: Prostacyclin and thromboxane A2 biosynthesis capacities of heart, arteries and platelets at various stages of experimental atherosclerosis in rabbits. Atherosclerosis 31, 385–394 (1978)
Hamberg, M., Svensson, J., Samuelsson, B.: Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc. Natl. Acad. Sci. USA 72, 2994–2998 (1975)
Harker, L. A., Ross, R., Glomset, J.: Role of the platelet in atherogenesis. Ann. N.Y. Acad. Sci. 275, 321–329 (1976)
Hidaka, H., Asano, T., Shimamoto, T.: Cyclic 3′:5′-AMP phosphodiesterase of rabbit aorta. Biochim. Biophys. Acta 377, 103–116 (1975)
Holmsen, H., Setkowsky, C. A., Day, H. J.: Effects of antimycin and 2-deoxyglucose on adenine nucleotides in human platelets. Role of metabolic adenosine triphosphate in primary aggregation, secondary aggregation and shape change of platelets. Biochem. J. 144, 385–396 (1974)
Ilien, B., Stierle, A., Lugnier, C., Stoclet, J. C., Landry, Y.: Separation of three cyclic nucleotide phosphodiesterases from bovine aorta. Biochem. Biophys. Res. Commun. 83, 486–492 (1978)
Kalbhen, D. A., Koch, H. J.: Methodische Untersuchungen zur quantitativen Mikrobestimmung von ATP in biologischem Material mit dem Firefly-Enzymsystem. Z. Klin. Chem. 5, 299–304 (1967)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol-reagent. J. Biol. Chem. 193, 265–275 (1951)
Moncada, S., Herman, A. G., Higgs, E. A., Vane, J. R.: Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the anti-thrombotic properties of vascular endothelium. Thromb. Res. 11, 323–344 (1977)
Moncada, S., Korbut, R.: Dipyridamole and other phosphodiesterase inhibitors act as antithrombotic agents by potentiating endogenous prostacyclin. Lancet II, 1286–1289 (1978)
Numano, F.: Progression and regression of atherosclerosis. Asian Med. J. 20, 625–644 (1977)
Numano, F., Maezawa, H., Shimamoto, T., Adachi, K.: Changes of cyclic AMP and cyclic AMP phosphodiesterase in the progression and regression of experimental atherosclerosis. Ann. N.Y. Acad. Sci. 275, 311–320 (1976)
Pastan, I., Johnson, G. S., Anderson, W. B.: Role of cyclic nucleotides in growth control. Annu. Rev. Biochem. 44, 491–522 (1975)
Pearson, J. D., Carleton, J. S., Hutchings, A., Gordon, J. L.: Uptake and metabolism of adenosine by pig aortic endothelial and smooth muscle cells in culture. Biochem. J. 170, 265–271 (1978)
Sixma, J. J., Lips, J. P. M., Trieschnigg, A. M. C., Holmsen, H.: Transport and metabolism of adenosine in human blood platelets. Biochim. Biophys. Acta 443, 33–48 (1976)
Summers, A., Subbarao, K., Rucinski, B., Niewiarowski, S.: The effect of dipyridamole on adenosine uptake by platelets ex vivo. Thromb. Res. 11, 611–618 (1977)
Tateson, J. E., Moncada, S., Vane, J. R.: Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins 13, 389–397 (1977)
Tornling, G., Unge, G., Ljungqvist, A., Carlsson, S.: Dipyridamole and capillary proliferation. A preliminary report. Acta Pathol. Microbiol. Scand. [A] 86, 82 (1978)
Zmuda, A., Dembinska-Kiec, A., Chytkowski, A., Gryglewski, R. J.: Experimental atherosclerosis in rabbits: Platelet aggregability, thromboxane A2 generation and anti-aggregatory potency of prostacyclin. Prostaglandins 14, 1035–1042 (1977)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dembinska-Kiec, A., Rücker, W. & Schönhöfer, P.S. Effects of dipyridamole in vivo on ATP and cAMP content in platelets and arterial walls and on atherosclerotic plaque formation. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 59–64 (1979). https://doi.org/10.1007/BF00498756
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00498756