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Acute Cadmium Exposure Reduces the Local Angiotensin I Converting Enzyme Activity and Increases the Tissue Metal Content

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Abstract

Cadmium exposure causes health problems that may result from increased oxidative stress and from changes in enzyme metalloproteases activities as angiotensin-converting enzyme (ACE). In fact, cadmium produces inhibition of serum ACE but is not known how cadmium acts on tissue ACE activity and whether following acute exposure tissue cadmium content is increased. In order to elucidate these issues, a cadmium bolus was injected intravenously in Wistar rats, and the cadmium content and the ACE activity were measured in the serum, lungs, aorta and kidneys. Moreover, in order to clarify if the cadmium affects directly tissue ACE activity, acute metal exposure in vitro was performed. Our results demonstrated that 120 min following cadmium administration, blood and organ cadmium content were both increased. Serum and lung ACE activity were reduced following acute cadmium exposure, but aortic and kidney ACE activities were not affected. The inhibitory effects induced by cadmium on ACE activity were also observed in the serum, as well as the lungs and the aorta, but not in the kidneys following in vitro exposure. Moreover, the inhibitory effects induced by cadmium on ACE activity were partially restored in vitro by zinc supplementation, suggesting a possible interaction or competition between cadmium and zinc by at the active site of ACE. Summarising, our results suggest that acute cadmium exposure promotes an increase in the tissue metal content that was accompanied by direct inhibition of serum, aorta and lung ACE activity, an effect that is cadmium concentration-dependent and is partially reversed by zinc.

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References

  1. Satarug S, Nishijo M, Ujjin P et al (2005) Cadmium-induced nephropathy in the development of high blood pressure. Toxicol Lett 157:57–68

    Article  CAS  PubMed  Google Scholar 

  2. Zhang W, Fievez L, Cheu E et al (2010) Anti-inflammatory effects of formoterol and ipratropium bromide against acute cadmium-induced pulmonary inflammation in rats. Eur J Pharmacol 628:171–178. doi:10.1016/j.ejphar.2009.11.015

    Article  CAS  PubMed  Google Scholar 

  3. Nishijo M, Morikawa Y, Nakagawa H et al (2006) Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment. Occup Environ Med 63:545–550. doi:10.1136/oem.2006.026591

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Nawrot TS, Van Hecke E, Thijs L et al (2008) Cadmium-related mortality and long-term secular trends in the cadmium body burden of an environmentally exposed population. Environ Health Perspect 116:1620–1628. doi:10.1289/ehp.11667

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Menke A, Muntner P, Silbergeld EK et al (2009) Cadmium levels in urine and mortality among U.S. adults. Environ Health Perspect 117:190–196. doi:10.1289/ehp.11236

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Vassallo DV, Simões MR, Furieri LB et al (2011) Toxic effects of mercury, lead and gadolinium on vascular reactivity. Brazilian J Med Biol Res 44:939–946. doi:10.1590/S0100-879X2011007500098

    Article  CAS  Google Scholar 

  7. Afridi HI, Kazi TG, Kazi NG et al (2010) Evaluation of cadmium, lead, nickel and zinc status in biological samples of smokers and nonsmokers hypertensive patients. J Hum Hypertens 24:34–43. doi:10.1038/jhh.2009.39

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. WHO World Health Organization. Cadmium (1992) Environmental Health Criteria 134. International Programme on Chemical Safety (IPCS), Geneve, Switzerland

  9. Satarug S, Baker JR, Urbenjapol S, et al (2003) A global perspective on cadmium pollution and toxicity in non-occupationally exposed population. Toxicol Lett pp 65–83

  10. Clemens S (2006) Toxic metal accumulation, responses to exposure and mechanisms of tolerance in plants. Biochimie 88:1707–1719. doi:10.1016/j.biochi.2006.07.003

    Article  CAS  PubMed  Google Scholar 

  11. Haswell-Elkins M, McGrath V, Moore M et al (2007) Exploring potential dietary contributions including traditional seafood and other determinants of urinary cadmium levels among indigenous women of a Torres Strait Island (Australia). J Expo Sci Environ Epidemiol 17:298–306. doi:10.1038/sj.jes.7500547

    Article  CAS  PubMed  Google Scholar 

  12. Copes R, Clark NA, Rideout K et al (2008) Uptake of cadmium from Pacific oysters (Crassostrea gigas) in British Columbia oyster growers. Environ Res 107:160–169. doi:10.1016/j.envres.2008.01.014

    Article  CAS  PubMed  Google Scholar 

  13. Satarug S, Garrett SH, Sens MA, Sens DA (2010) Cadmium, environmental exposure, and health outcomes. Environ Health Perspect 118:182–190. doi:10.1289/ehp.0901234

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Abu-Hayyeh S, Sian M, Jones KG et al (2001) Cadmium accumulation in aortas of smokers. Arterioscler Thromb Vasc Biol 21:863–867. doi:10.1161/01.ATV.21.5.863

    Article  CAS  PubMed  Google Scholar 

  15. Idée JM, Port M, Raynal I et al (2006) Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundam Clin Pharmacol 20:563–576. doi:10.1111/j.1472-8206.2006.00447.v

    Article  PubMed  Google Scholar 

  16. Sturrock ED, Natesh R, van Rooyen JM, Acharya KR (2004) Structure of angiotensin I-converting enzyme. Cell Mol Life Sci 61:2677–2686. doi:10.1007/s00018-004-4239-0

    Article  CAS  PubMed  Google Scholar 

  17. Lee MA, Paul M, Böhm M, Ganten D (1992) Effects of angiotensin-converting enzyme inhibitors on tissue renin-angiotensin systems. Am J Cardiol 70:12C–19C. doi:10.1016/0002-9149(92)91353-6

    Article  CAS  PubMed  Google Scholar 

  18. Simões MR, Ribeiro Júnior RF, Vescovi MV et al (2011) Acute lead exposure increases arterial pressure: role of the renin-angiotensin system. PLoS One 6:e18730. doi:10.1371/journal.pone.0018730

    Article  PubMed Central  PubMed  Google Scholar 

  19. Sharifi AM, Darabi R, Akbarloo N et al (2004) Investigation of circulatory and tissue ACE activity during development of lead-induced hypertension. Toxicol Lett 153:233–238. doi:10.1016/j.toxlet.2004.04.013

    Article  CAS  PubMed  Google Scholar 

  20. Puri VN (1992) Acute effects of cadmium on the renin angiotensin system in rats. Biochem Pharmacol 44:187–188. doi:10.1016/0006-2952(92)90056-O

    Article  CAS  PubMed  Google Scholar 

  21. Puri VN, Saha S (2003) Comparison of acute cardiovascular effects of cadmium and captopril in relation to oxidant and angiotensin converting enzyme activity in rats. Drug Chem Toxicol 26:213–218. doi:10.1081/DCT-120022646

    Article  CAS  PubMed  Google Scholar 

  22. Samani NJ, Morgan K, Brammar WJ, Swales JD (1987) Detection of renin messenger RNA in rat tissues: increased sensitivity using an RNAse protection technique. J Hypertens Suppl 5:S19–S21

    Article  CAS  PubMed  Google Scholar 

  23. Suzuki F, Ludwig G, Hellmann W et al (1988) Renin gene expression in rat tissues: a new quantitative assay method for rat renin mRNA using synthetic cRNA. Clin Exp Hypertens A 10:345–359. doi:10.3109/10641968809103531

    Article  CAS  PubMed  Google Scholar 

  24. Friedland J, Silverstein E (1976) A sensitive fluorimetric assay for serum angiotensin-converting enzyme. Am J Clin Pathol 66:416–424

    CAS  PubMed  Google Scholar 

  25. (ATSDR) Agency for Toxic Substances and Disease Registry (2008) Toxocological profile for cadmium

  26. Varoni MV, Palomba D, Macciotta NP et al (2010) Brain renin-angiotensin system modifies the blood pressure response to intracerebroventricular cadmium in rats. Drug Chem Toxicol 33:302–309. doi:10.3109/01480540903418496

    Article  CAS  PubMed  Google Scholar 

  27. Puri VN, Sur RN (1986) Effect of cadmium clonidine interaction in rats. Pharmacol Res Commun 18:1119–1122. doi:10.1016/0031-6989(86)90027-5

    Article  CAS  PubMed  Google Scholar 

  28. Lee MA, Paul M, Böhm M et al (1992) Effects of angiotensin-converting enzymei inhibitors on tissue renin-angiotensin systems. Am J Cardiol 70(10):12c–19c

    Article  CAS  PubMed  Google Scholar 

  29. Sparks MA, Crowley SD, Gurley SB et al (2014) Classical renin-angiotensin system in kidney physiology. Compr Physiol 4:1201–28. doi:10.1002/cphy.c130040

    Article  PubMed Central  PubMed  Google Scholar 

  30. Fyhrquist F, Saijonmaa O (2008) Renin-angiotensin system revisited. J Intern Med 264:224–236. doi:10.1111/j.1365-2796.2008.01981.x

    Article  CAS  PubMed  Google Scholar 

  31. Nakamura Y, Nakamura K, Matsukura T (1988) Vascular angiotensin converting enzyme activity in spontaneously hypertensive rats and its inhibition with cilazapril. J Hypertens 6:105–110

    CAS  PubMed  Google Scholar 

  32. Angeli JK, Cruz Pereira CA, de Oliveira FT et al (2013) Cadmium exposure induces vascular injury due to endothelial oxidative stress: the role of local angiotensin II and COX-2. Free Radic Biol Med 65:838–48. doi:10.1016/j.freeradbiomed.2013.08.167

    Article  CAS  PubMed  Google Scholar 

  33. Saxena PR (1992) Interaction between the renin-angiotensin-aldosterone and sympathetic nervous systems. J Cardiovasc Pharmacol 19(Suppl 6):S80–S88. doi:10.1097/00005344-199219006-00013

    Article  CAS  PubMed  Google Scholar 

  34. Unger T, Ganten D, Lang RE (1987) Effect of converting enzyme inhibitors on tissue converting enzyme and angiotensin II: therapeutic implications. Am J Cardiol 59:18D–22D. doi:10.1016/0002-9149(87)90047-6

    Article  CAS  PubMed  Google Scholar 

  35. Ripa S, Ripa R (1994) Zinc and arterial pressure. Minerva Med 85:455–459

    CAS  PubMed  Google Scholar 

  36. Corot C, Idee JM, Hentsch AM et al (1998) Structure-activity relationship of macrocyclic and linear gadolinium chelates: investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme. J Magn Reson Imaging 8:695–702. doi:10.1002/jmri.1880080328

    Article  CAS  PubMed  Google Scholar 

  37. Carvalho E, Göthe PO, Bauer R et al (1995) Effect of inhibitors on the coordination geometries of cadmium at the metal sites in angiotensin-I-converting enzyme. Eur J Biochem 234:780–785

    Article  CAS  PubMed  Google Scholar 

  38. Balaraman R, Gulati OD, Bhatt JD et al (1989) Cadmium-induced hypertension in rats. Pharmacology 38:226–234. doi:10.1159/000138541

    Article  CAS  PubMed  Google Scholar 

  39. Skoczynska A, Stojek E (2005) The impact of subchronic lead poisoning on the vascular effect of nitric oxide in rats. Environ Toxicol Pharmacol 19:99–106. doi:10.1016/j.etap.2004.05.004

    Article  CAS  PubMed  Google Scholar 

  40. Houston M (2007) The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction. Altern Ther Heal Med 128–134

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Acknowledgmets

This project was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and CNPq/FAPES (Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Espírito Santo) (54668662/2011). The funders had no role in the study’s design, data collection or analysis nor were they involved in the manuscript’s preparation or the decision to publish it.

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Authors and Affiliations

  1. Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, Maruípe, Vitória, ES, 29040-091, Brazil

    Gilson B. Broseghini-Filho, Camila C. Pereira Almenara, Marcus V. A. Vescovi, Thaís de O. Faria, Dalton V. Vassallo, Jhuli K. Angeli & Alessandra S. Padilha

  2. Escola de Ensino Superior da Santa Casa de Misericórdia de Vitória, EMESCAM, Vitória, ES, Brazil

    Dalton V. Vassallo

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  1. Gilson B. Broseghini-Filho
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  2. Camila C. Pereira Almenara
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  3. Marcus V. A. Vescovi
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Correspondence to Gilson B. Broseghini-Filho.

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Broseghini-Filho, G.B., Almenara, C.C.P., Vescovi, M.V.A. et al. Acute Cadmium Exposure Reduces the Local Angiotensin I Converting Enzyme Activity and Increases the Tissue Metal Content. Biol Trace Elem Res 166, 149–156 (2015). https://doi.org/10.1007/s12011-015-0250-6

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  • DOI: https://doi.org/10.1007/s12011-015-0250-6

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