Abstract
The effect of cadmium chloride (CdCl2) on cell proliferation and EDRF (endothelium-derived relaxing factor) production by cultured human umbilical arterial endothelial cells (HUAECs) was investigated. The viability of HUAECs decreased dose-dependently after the addition of Cd (cadmium chloride). Morphologic examination by phase contrast microscopy revealed severe damaging effects of Cd at higher concentrations. The cytotoxic effect of Cd on DNA synthesis was also concentration-dependent. The effect of Cd on EDRF production by indomethacin-treated HUAECs was assessed by its anti-platelet aggeragory effect. Platelet aggregation studies were carried out in cuvettes lined with HUAECs using an aggregometer. The anti-platelet aggregatory effect was decreased dose-dependently by pretreatment with Cd. These findings suggest that HUAECs are susceptible to concentration-dependent Cd cytotoxicity, and that Cd can inhibit the production of EDRF by HUAECs.
Similar content being viewed by others
References
Azuma H, Ishikawa M, Sekizaki S (1986) Endothelium-dependent inhibition of platelet aggregation. Br J Pharmacol 88: 411–415
Engvall J, Perk J (1985) Prevalence of hypertension among cadmium-exposed workers. Arch Environ Health 40: 185–190
Evans RM, Patierno SR, Wang D (1983) Growth inhibition and methallothionein induction in cadmium-resistant cells by essential and non-essential metals. Mol Pharmacol 24: 77–83
Forstermann U, Pollock S, Schmidt HHHW, Heller M, Murad F (1991) Calmodulin-dependent endothelium-derived relaxing factor/nitric oxide synthase activity is present in the particular and cytosolic fraction of bovine aortic endothelial cells. Proc Natl Acad Sci USA 88: 1788–1792
Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 228: 373–376
Ignaro JL (1989) Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein. Circ Res 65: 1–21
Jacobson KJ, Dethlefsen LA (1980) The interaction of cadmium and certain other metal ions with proteins ands nucleic acids. Toxicology 16: 1–37
Kishimoto T, Fukuzawa Y, Tada M (1982) Studies human vascular endothelial cells; Basic attempt to primary cell culture. Bull Shimane Med Univ 5: 23–28 (in Japanese with English abstract)
Kishimoto T (1987) The effect of antifebriles on human vascular endothelial cells at high temperature in cell culture. Jpn J Biometeor 24: 117–124 (in Japanese with English abstract)
Kishimoto T, Okazaki M, Fukuzawa Y, Tada M (1985a) The effects of cadmium on the adhesion and growth of normal and malignant human cells at high temperatures. Shimane J Med Sci 9: 60–68
Kishimoto T, Fukuzawa Y, Abe M, Hashimoto M, Tada M (1985b) Assessment of endothelium-derived relaxing factor from human coronary arteries using the anti-platelet aggregory effect. Jpn J Hyg 46: 1043–1050
Lauwerys R (1979) Cadmium in man. In: Webb M (ed) The chemistry, biochemistry and biology of cadmium. Elsevier North Holland, Amsterdam, pp 433–442
Lidbury PS, Thiemermann C, Thomas G R (1989) Endothelin-3: selectivity as an anti-aggregatory peptide in vivo. Eur J Pharmacol 166: 335–338
Luscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertenson 8: 344–348
Luscher TF, Raji L, Vanhoutte PM (1987) Endothelium-dependent vascular responses in normotensive and hypertensive dahl rats. Hypertension 9: 157–163
Luscher TF, Diederich D, Weber E (1988) Endothelium-dependent responses in carotid and renal arteries of normotensive and hypertensive rats. Hypertension 11: 573–578
Moncada S, Gryglewsky R, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–665
Morselt AW, Peereboom-Stegman C, Jongstra-Spaan EJ (1983a) Investigation for the mechanism of cadmium toxicity at cellular level; 1. A light microscopical study. Arch Toxicol 52: 91–97
Morselt AW, Peereboom-Stegman C, Jongstra-Spaapen EJ (1983b) Investigation for the mechanism of cadmium toxicity at cellular level; II. An electron microscopical study. Arch Toxicol 52: 99–108
Nishiyama S, Nakamura K, Konishi Y (1987) Effect of selenium on blood pressure, urinary sodium excretion and plasma aldosterone in cadmium-treated male rats. Arch Toxicol 59: 365–370
Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526
Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesyze nitric oxide from 1-arginine. Nature 333: 664–666
Perry MH, Erlanger WM, Perry FE (1983) Effect of a second metal on cadmium-induced hypertension. Arch Environ Health 38: 80–85
Puri NV, Sur NR (1983) Cardiovascular effects of cadmium on intravenous and intracerebroventricular administration in rats. Can J Physiol Pharmacol 61: 1430–1432
Rapoport RM, Draznin MB, Murad F (1983) Endothelium-dependent relaxation in rat aorta may be mediated through cyclic GMP-dependent protein phosphorylation. Nature 306: 174–176
Ross R, Glomset AJ (1976a) The pathogenesis of atherosclerosis (first of two parts). N Engl J Med 295: 369–420
Ross R, Glomset AJ (1976b) The pathogenesis of atherosclerosis (second part). N Engl J Med 295: 420–425
Samarawickrama GP (1979) Cadmium in man. In: Webb M (ed) Biological effects of cadmium in mammals. Elsevier North Holland, Amsterdam, pp 341–356
Stein O, Stein Y (1980) Bovine aortic endothelial cells display macrophage-like properties towards acetylated 125I-labelled low density lipoprotein. Biochim Biophys Acta 620: 631–635
Sugimoto T, Tobian L, Ganguli MC (1988) High potassium diets protect against dysfunction of endothelial cells in stroke-prone spontaneously hypertensive rats. Hypertension 11: 579–585
Tateston JE, Moncada S, Vane JR (1977) Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins 13: 389–397
Thiemermann C, Lidbury PS, Thomas GR (1989) Endothelin-1 releses prostacyclin and inhibits ex vivo platelet aggregation in the anesthetized rabbit. J Cardiovasc Pharmacol 13: S138-S141
Voyta JC, Netland PA, Via DP, Zetter BR (1984) Specific labelling of endothelial cells using fluorescent acetylated-low density lipoprotein. J Cell Biology 99: 81A
Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–414
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kishimoto, T., Oguri, T., Ohno, M. et al. Effect of cadmium (CdCl2) on cell proliferation and production of EDRF (endothelium-derived relaxing factor) by cultured human umbilical arterial endothelial cells. Arch Toxicol 68, 555–559 (1994). https://doi.org/10.1007/s002040050113
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s002040050113