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Increase in number of Weibel-Palade bodies and endothelin-1 release from endothelial cells in the cadmium-treated rat thoracic aorta

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Abstract

Male rats received daily intraperitoneal injections of cadmium sulphate (2.0 mg/kg) for 3 (Cd-3 group), 6 (Cd-6 group) and 8 days (Cd-8 group). The blood samples were prepared for endothelin (ET)-1 assay, and the thoracic aorta was investigated by both electron microscopy and immunoelectron microscopy using anti ET-1 sera. The plasma ET-1 concentrations of both Cd-6 and Cd-8 groups increased significantly in a cumulative dose-dependent manner. The cadmium-treated rat aorta showed an increase in the number of Weibel-Palade (WP) bodies in endothelial cells, and degranulation and exocytosis of WP bodies occurred exclusively in the Cd-8 group. Immunoreaction for ET-1 was localized preferentially in WP bodies of both cadmium-treated and control groups, and in the rough endoplasmic reticulum of the cadmium-treated groups only. Reactivity was also found on the WP bodies undergoing exocytosis in the Cd-8 group. Cadmium intoxication induces an increase in number of ET-1-storing WP bodies in the rat aorta endothelium. The enhancement of extracellular release of their contents by exocytosis results in elevation of the plasma ET-1 concentration.

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References

  1. Bertini F, Santolaya R (1970) A novel type of granules observed in toad endothelial cells and their relationship with blood pressure active factors. Experientia 26:522–523

    Google Scholar 

  2. Bonfanti R, Furie BC, Furie B, Wagner DD (1989) PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood 73:1109–1112

    Google Scholar 

  3. Chin TA, Templeton DM (1992) Effects of CdCl2 and Cd-metallothionein on cultured mesangial cells. Toxicol Appl Pharmacol 116:133–141

    Google Scholar 

  4. Doi Y, Fujimoto S (1993) Vasocontractions of the in-vitro toad aortas induced by endothelin-1 and sarafotoxin-S6b. Anat Rec 235:253–260

    Google Scholar 

  5. Doi Y, Ozaka T, Katsuki M, Fukushige H, Toyama E, Kanazawa Y, Arashidani K, Fujimoto S (1995) Histamine release from Weibel-Palade bodies of toad aortas induced by endothelin-1 and sarafotoxin-S6b. Anat Rec 242:374–382

    Google Scholar 

  6. Engvall J, Perk J (1985) Prevalence of hypertension among cadmium-exposed workers. Arch Environ Health 40:185–190

    Google Scholar 

  7. Evans DH, Weingarten K (1990) The effect of cadmium and other metals on vascular smooth muscle of the dogfish shark, Squalus acanthias. Toxicology 61:275–281

    Google Scholar 

  8. Fujimori A, Yanagisawa M, Saito A, Goto K, Masaki T, Mima T, Takakura K, Shigeno T (1990) Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage. Lancet 336:633

    Google Scholar 

  9. Fujimoto S, Yamamoto K, Arashidani K, Hayabuchi I, Yoshizuka M, Nomiyama T (1982) Endothelial specific granules in the umbilical veins of the postnatal rabbit. Cell Tissue Res 227:509–518

    Google Scholar 

  10. Hirata Y, Itoh K, Ando K, Endo M, Marumo F (1989) Plasma endothelin levels during surgery. N Engl J Med 321:1686

    Google Scholar 

  11. Ishibashi M, Saito K, Watanabe K, Uesugi S, Furue H, Yamaji T (1991) Plasma endothelin-1 levels in patients with disseminated intravascular coagulation. N Engl J Med 324:1516–1517

    Google Scholar 

  12. Kagawa H, Fujimoto S (1987) Electron-microscopic and immunocytochemical analyses of Weibel-Palade bodies in the human umbilical vein during pregnancy. Cell Tissue Res 249:557–563

    Google Scholar 

  13. Kohno M, Yasunari K, Murakawa K, Yokokawa K, Horio T, Fukui T, Takeda T (1990) Plasma immunoreactive endothelin in essential hypertension. Am J Med 88:614–618

    Google Scholar 

  14. Kon V, Sugiura M, Inagami T, Harvie BR, Ichikawa I, Hoover RL (1990) Role of endothelin in cyclosporine-induced glomerular dysfunction. Kidney Int 37:1487–1491

    Google Scholar 

  15. Lanese DM, Conger JD (1993) Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles. J Clin Invest 91:2144–2149

    Google Scholar 

  16. McEver RP, Beckstead JH, Moore KL, Marshall-Carison L, Bainton DF (1989) GMP-140, a platelet a-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 84:92–99

    Google Scholar 

  17. Mclean IW, Nakane PK (1974) Periodate-lysine-paraformaldehyde fixative: a new fixative for immunoelectron microscopy. J Histochem Cytochem 22:1077–1083

    CAS  PubMed  Google Scholar 

  18. Morel DR, Lacroix JS, Hemsen A, Steinig DA, Pittet JF, Lundberg JM (1989) Increased plasma and pulmonary lymph levels of endothelin during endotoxin shock. Eur J Pharmacol 167:427–428

    Google Scholar 

  19. Morita T, Kurihara H, Yoshizumi M, Takaku F, Machii K, Yazaki Y (1989) Effects of polymorphonuclear leukocytes on endothelin production by vascular endothelial cells. Circulation 80:II-584

    Google Scholar 

  20. Murakami M, Webb M (1981) A morphological and biochemical study of the effects of l-cysteine on the renal uptake and nephrotoxicity of cadmium. Br J Exp Pathol 62:115–130

    Google Scholar 

  21. Nakamura S, Naruse M, Naruse K, Demura H, Uemura H (1990) Immunocytochemical localization of endothelin in cultured bovine endothelial cells. Histochemistry 94:475–477

    Google Scholar 

  22. 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

    Google Scholar 

  23. Niwa A, Suzuki A (1982) Effects of cadmium on the tension of isolated rat aorta (a possible mechanism for cadmium-induced hypertension). J Toxicol Sci 7:51–60

    Google Scholar 

  24. Nolan CV, Shaikh ZA (1986) The vascular endothelium as a target tissue in acute cadmium toxicity. Life Sci 39:1403–1409

    Google Scholar 

  25. Puri VN, Sur RN (1983) Cardiovascular effects of cadmium on intravenous and intracerebroventricular administration in rats. Can J Physiol Pharmacol 61:1430–1432

    Google Scholar 

  26. Revis NW, Zinsmeister AR, Bull R (1981) Atherosclerosis and hypertension induction by lead and cadmium ions: an effect prevented by calcium ion. Proc Natl Acad Sci USA 78:6494–6498

    Google Scholar 

  27. Ross R (1981) Atherosclerosis: a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis 1:293–311

    Google Scholar 

  28. Ross R, Glomset JA (1976) The pathogenesis of atherosclerosis. N Engl J Med 295:369–377, 420–425

    Google Scholar 

  29. Saito Y, Nakao K, Mukoyama M, Imura H (1990) Increased plasma endothelin level in patients with essential hypertension. N Engl J Med 322:205

    Google Scholar 

  30. Sakamoto Y, Doi Y, Ohsato K, Fujimoto S (1993) Immunoelectron microscopy on the localization of endothelin in the umbilical vein of perinatal rabbits. Anat Rec 237:482–488

    Google Scholar 

  31. Samarawickrama GP, Webb M (1979) Acute effects of cadmium on the pregnant rat and embryo-fetal development. Environ Health Perspect 28:245–249

    Google Scholar 

  32. Schroeder HA, Vinton WH Jr (1962) Hypertension induced in rats by small doses of cadmium. Am J Physiol 202:515–518

    Google Scholar 

  33. Shigeno T, Mima T, Yanagisawa M, Saito A, Goto K, Yamashita K, Takenouchi T, Matsuura N, Yamasaki Y, Yamada K, Masaki T, Takakura K (1991) Prevention of cerebral vasospasm by actinomycin D. J Neurosurg 74:940–943

    Google Scholar 

  34. Sugiura M, Inagami T, Kon V (1989) Endotoxin stimulates endothelin-release in vivo and in vitro as determined by radioimmunoassay. Biochem Biophys Res Commun 161:1220–1227

    Google Scholar 

  35. Suzuki N, Matsumoto H, Kitada C, Masaki T, Fujino M (1989) A sensitive sandwich-enzyme immunoassay for human endothelin. J Immunol Methods 118:245–250

    Google Scholar 

  36. Toyo-oka T, Aizawa T, Suzuki N, Hirata Y, Miyauchi T, Shin WS, Yanagisawa M, Masaki T, Sugimoto T (1991) Increased plasma level of endothelin-1 and coronary spasm induction in patients with vasospastic angina pectoris. Circulation 83:476–483

    Google Scholar 

  37. Wagner DD, Olmsted JB, Marder VJ (1982) Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol 95:355–360

    Google Scholar 

  38. Watari N, Hotta Y, Mabuchi Y (1989) Ultrastructural studies on a cadmium-storing cell in rat pancreatic tissues following cadmium chloride administration. J Electron Microsc 38:235–241

    Google Scholar 

  39. Weibel ER, Palade GE (1964) New cytoplasmic components in arterial endothelia. J Cell Biol 23:101–112

    Google Scholar 

  40. 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 332:411–415

    Article  PubMed  Google Scholar 

  41. Yanagisawa M, Inoue A, Ishikawa T, Kasuya Y, Kimura S, Kumagaye S, Nakajima K, Watanabe TX, Sakakibara S, Goto K, Masaki T (1988) Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci USA 85:6964–6967

    Google Scholar 

  42. Yoshizuka M, Tanaka I, Mori N, Maruyama T, Hirano T, Doi Y, Kawahara A, Miyazaki M, Fujimoto S (1990) Cadmium toxicity on the thoracic aorta of pregnant rats: electron microscopy and x-ray microanalysis. Biomed Res (India) 1:11–17

    Google Scholar 

  43. Yoshizuka M, Hamasaki K, Tanaka I, Yokoyama M, Doi Y, Hara K, Mori N, Miyazaki M, Fujimoto S (1992) The effect of cadmium toxicity on the uterine blood vessels of pregnant rats. Biomed Res (India) 3:181–187

    Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy, University of Occupational and Environmental Health, School of Medicine, 807, Kitakyushu, Japan

    Y. Doi, T. Ozaka, H. Fukushige & S. Fujimoto

  2. Department of Nursing, University of Occupational and Environmental Health, School of Health Sciences, 807, Kitakyushu, Japan

    H. Furukawa

  3. Department of Anatomy, Kurume University School of Medicine, 830, Kurume, Japan

    M. Yoshizuka

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  1. Y. Doi
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  2. T. Ozaka
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  3. H. Fukushige
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  4. S. Fujimoto
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  5. H. Furukawa
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  6. M. Yoshizuka
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Doi, Y., Ozaka, T., Fukushige, H. et al. Increase in number of Weibel-Palade bodies and endothelin-1 release from endothelial cells in the cadmium-treated rat thoracic aorta. Vichows Archiv A Pathol Anat 428, 367–373 (1996). https://doi.org/10.1007/BF00202203

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  • DOI: https://doi.org/10.1007/BF00202203

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