Skip to main content
Log in

Short-term Effects of Cadmium Exposure on Blood Pressure and Vascular Function in Wistar Rats

  • Research
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Chronic cadmium exposure is known to be associated with vascular changes and increased blood pressure, but its short-term effects on the cardiovascular system remain poorly understood. This study aimed to investigate the pressoric and vascular effects of a 7-day exposure to CdCl2 in Wistar rats. The rats were divided in control group (Ct), which received tap water, and the Cd group, which received a 100 mg/L CdCl2 solution via drinking water for 7 days. We analyzed body weight, plasma Cadmium concentration, systolic blood pressure (SBP), and vascular responses. Despite relatively low plasma Cadmium concentration, the Cd group exhibited elevated SBP and increased contractile response to phenylephrine. Endothelium removal and NOS inhibition increased contractions in both groups. In the Cd group's aorta, we observed enhanced levels of phospho-eNOS (Ser1177) and basal NO release. Cd group showed reduced Catalase expression and increased basal release of H2O2, with catalase reducing the contractile response. In arteries pre-contracted with phenylephrine, Cd group showed impaired endothelium-dependent (Acetylcholine) and independent (sodium nitroprussiate—SNP) relaxation responses. However, responses to SNP were similar after pre-contraction with KCl in both groups. These data suggest early effects of Cadmium on blood pressure and aortic function, indicating impaired H2O2-scavenging by catalase. Increased H2O2 due to Cadmium exposure might explain heightened responses to phenylephrine and weakened relaxation responses mediated by the NO-K+-channels pathway. Our findings shed light on Cadmium's short-term impact on the cardiovascular system, providing insights into potential mechanisms underlying its effects on blood pressure regulation and vascular function.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

Data associated with this study are available upon request to the corresponding author. For access to the raw data, analysis code, and other relevant materials supporting the findings of this study, please contact us at alessandra.padilha@ufes.br. Data will be provided in accordance with our institution's data sharing policies and will be made available for review and replication purposes.

References

  1. Bilgen I, Öner G, Edremitlioglu M et al (2003) Involvement of cholinoceptors in cadmium-induced endothelial dysfunction. J Basic Clin Physiol Pharmacol 14(1):55–76. https://doi.org/10.1515/JBCPP.2003.14.1.55

    Article  CAS  PubMed  Google Scholar 

  2. Almenara CCP, Broseghini-Filho GB, Vescovi MVA et al (2013) Chronic Cadmium Treatment Promotes Oxidative Stress and Endothelial Damage in Isolated Rat Aorta. PLoS ONE 8:e68418. https://doi.org/10.1371/journal.pone.0068418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Santamaria-Juarez C, Atonal-Flores F, Diaz A et al (2022) Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production. Arch Physiol Biochem 128(3):748–756. https://doi.org/10.1080/13813455.2020.1726403

    Article  CAS  PubMed  Google Scholar 

  4. Tzotzes V, Tzilalis V, Giannakakis S et al (2007) Effects of Acute and Chronic Cadmium Administration on the Vascular Reactivity of Rat Aorta. Biometals 20:83–91. https://doi.org/10.1007/s10534-006-9017-z

    Article  CAS  PubMed  Google Scholar 

  5. Sompamit K, Kukongviriyapan U, Donpunha W et al (2010) Reversal of cadmium-induced vascular dysfunction and oxidative stress by meso-2,3-dimercaptosuccinic acid in mice. Toxicol Lett 198:77–82. https://doi.org/10.1016/j.toxlet.2010.04.007

    Article  CAS  PubMed  Google Scholar 

  6. Donpunha W, Kukongviriyapan U, Sompamit K et al (2011) Protective effect of ascorbic acid on cadmium-induced hypertension and vascular dysfunction in mice. Biometals 24:105–115. https://doi.org/10.1007/s10534-010-9379-0

    Article  CAS  PubMed  Google Scholar 

  7. Yoopan N, Wongsawatkul O, Watcharasit P et al (2006) Contribution of cholinergic muscarinic functions in cadmium-induced hypertension in rats. Toxicol Lett 164:S155. https://doi.org/10.1016/j.toxlet.2006.06.322

    Article  Google Scholar 

  8. Kukongviriyapan U, Pannangpetch P, Kukongviriyapan V et al (2014) Curcumin protects against cadmium-induced vascular dysfunction, hypertension and tissue cadmium accumulation in mice. Nutrients 6:1194–1208. https://doi.org/10.3390/nu6031194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sangartit W, Kukongviriyapan U, Donpunha W et al (2014) Tetrahydrocurcumin Protects against Cadmium-Induced Hypertension, Raised Arterial Stiffness and Vascular Remodeling in Mice. PLoS ONE 9:e114908. https://doi.org/10.1371/journal.pone.0114908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fadloun Z, Leach GDH (1980) The effects of Cd2+ on the myogenic activity and the responsiveness of the rat portal vein to perimural stimulation, noradrenaline and potassium ions. Br J Pharmacol 68:181

    Google Scholar 

  11. Yoopan N, Watcharasit P, Wongsawatkul O et al (2008) Attenuation of eNOS expression in cadmium-induced hypertensive rats. Toxicol Lett 176:157–161. https://doi.org/10.1016/j.toxlet.2007.11.002

    Article  CAS  PubMed  Google Scholar 

  12. Fujiwara Y, Watanabe S, Kaji T (1998) Promotion of cultured vascular smooth muscle cell proliferation by low levels of cadmium. Toxicol Lett 94:175–180. https://doi.org/10.1016/S0378-4274(98)00005-8

    Article  CAS  PubMed  Google Scholar 

  13. Majumder S, Muley A, Kolluru GK et al (2008) Cadmium reduces nitric oxide production by impairing phosphorylation of endothelial nitric oxide synthase. Biochem Cell Biol 86:1–10. https://doi.org/10.1139/O07-146

    Article  CAS  PubMed  Google Scholar 

  14. Rossi EM, Ávila RA, Carneiro MTWD et al (2020) Chronic Iron Overload Restrains the Benefits of Aerobic Exercise to the Vasculature. Biol Trace Elem Res 198:521–534. https://doi.org/10.1007/s12011-020-02078-y

    Article  CAS  PubMed  Google Scholar 

  15. Somberg LB, Gutterman DD, Miura H et al (2017) Shock associated with endothelial dysfunction in omental microvessels. Eur J Clin Invest 47:30–37. https://doi.org/10.1111/eci.12697

    Article  CAS  PubMed  Google Scholar 

  16. Martelli A, Rousselet E, Dycke C et al (2006) Cadmium toxicity in animal cells by interference with essential metals. Biochimie 88:1807–1814

    Article  CAS  PubMed  Google Scholar 

  17. Horowitz A, Menice CB, Laporte R, Morgan KG (1996) Mechanisms of smooth muscle contraction. Physiol Rev 76:967–1003. https://doi.org/10.1152/physrev.1996.76.4.967

    Article  CAS  PubMed  Google Scholar 

  18. Faro AR, Pinto Wde J, Ferreira AP, Barbosa F Jr, Souza VC, Fujimoto DE, Koifman RJ, Koifman S (2014) Serum cadmium levels in a sample of blood donors in the Western Amazon, Brazil, 2010–2011. Cad Saude Publica 30(2):403–14. https://doi.org/10.1590/0102-311X00087113

    Article  PubMed  Google Scholar 

  19. Sadeghi N, Oveisi MR, Jannat B et al (2014) The relationship between bone health and plasma zinc, copper lead and cadmium concentration in osteoporotic women. J Environ Health Sci Eng 12:125. https://doi.org/10.1186/s40201-014-0125-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ishola AB, Okechukwu IM, Ashimedua UG et al (2017) Serum level of lead, zinc, cadmium, copper, and chromium among occupationally exposed automobile workers in Benin city. Int J Environ Poll Res 5:70–79

    Google Scholar 

  21. Satarug S, Nishijo M, Ujjin P et al (2005) Cadmium-induced nephropathy in the development of high blood pressure. Toxicol Lett 157:57–68. https://doi.org/10.1016/j.toxlet.2005.01.004

    Article  CAS  PubMed  Google Scholar 

  22. Balaraman R, Gulati OD, Rathod SP, Bhatt JD (1989) The acute pressor response to cadmium in rats. Arch Int Pharmacodyn Ther 301:254–266

    CAS  PubMed  Google Scholar 

  23. 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 Radical Biol Med 65:838–848. https://doi.org/10.1016/j.freeradbiomed.2013.08.167

    Article  CAS  Google Scholar 

  24. Brune B, Schmidt K-U, Ullrich V (1990) Activation of soluble guanylate cyclase by carbon monoxide and inhibition by superoxide anion. Eur J Biochem 192:683–688. https://doi.org/10.1111/j.1432-1033.1990.tb19276.x

    Article  CAS  PubMed  Google Scholar 

  25. Kawashima S, Yokoyama M (2004) Dysfunction of Endothelial Nitric Oxide Synthase and Atherosclerosis. Arterioscler Thromb Vasc Biol 24:998–1005. https://doi.org/10.1161/01.ATV.0000125114.88079.96

    Article  CAS  PubMed  Google Scholar 

  26. Dhalla NS, Temsah RM, Netticadan T (2000) Role of oxidative stress in cardiovascular diseases. J Hypertens 18:655–673. https://doi.org/10.1097/00004872-200018060-00002

    Article  CAS  PubMed  Google Scholar 

  27. Zhen J, Lu H, Wang XQ et al (2008) Upregulation of Endothelial and Inducible Nitric Oxide Synthase Expression by Reactive Oxygen Species. Am J Hypertens 21:28–34. https://doi.org/10.1038/ajh.2007.14

    Article  CAS  PubMed  Google Scholar 

  28. Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H Oxidase. Circ Res 86:494–501. https://doi.org/10.1161/01.RES.86.5.494

    Article  CAS  PubMed  Google Scholar 

  29. Zafar AM, Ushio-Fukai M, Akers M et al (1998) Role of NADH/NADPH Oxidase-Derived H2O2 in Angiotensin II–Induced Vascular Hypertrophy. Hypertension 32:488–495. https://doi.org/10.1161/01.HYP.32.3.488

    Article  Google Scholar 

  30. Touyz RM, Schiffrin EL (2004) Reactive oxygen species in vascular biology: implications in hypertension. Histochem Cell Biol 122:339–352. https://doi.org/10.1007/s00418-004-0696-7

    Article  CAS  PubMed  Google Scholar 

  31. Wang J, Zhang H, Zhang T et al (2015) Molecular mechanism on cadmium-induced activity changes of catalase and superoxide dismutase. Int J Biol Macromol 77:59–67. https://doi.org/10.1016/j.ijbiomac.2015.02.037

    Article  CAS  PubMed  Google Scholar 

  32. Shukla GS, Hussain T, Srivastava RS, Chandra SV (1989) Glutathione peroxidase and catalase in liver, kidney, testis and brain regions of rats following cadmium exposure and subsequent withdrawal. Ind Health 27:59–69. https://doi.org/10.2486/indhealth.27.59

    Article  CAS  PubMed  Google Scholar 

  33. Casalino E, Calzaretti G, Sblano C, Landriscina C (2002) Molecular inhibitory mechanisms of antioxidant enzymes in rat liver and kidney by cadmium. Toxicology 179:37–50. https://doi.org/10.1016/S0300-483X(02)00245-7

    Article  CAS  PubMed  Google Scholar 

  34. Salovsky P, Shopova V, Dancheva V, Marev R (1992) Changes in antioxidant lung protection after single intra-tracheal cadmium acetate instillation in rats. Hum Exp Toxicol 11:217–222. https://doi.org/10.1177/096032719201100310

    Article  CAS  PubMed  Google Scholar 

  35. Madeddu P, Demontis MP, Varoni MV et al (1993) Verapamil Prevents the Acute Hypertensive Response to Intracerebroventricular Cadmium in Conscious Normotensive Rats. Am J Hypertens 6:193–197. https://doi.org/10.1093/ajh/6.3.193

    Article  CAS  PubMed  Google Scholar 

  36. Oliveira TF, Batista PR, Leal MA et al (2019) Chronic Cadmium Exposure Accelerates the Development of Atherosclerosis and Induces Vascular Dysfunction in the Aorta of ApoE−/− Mice. Biol Trace Elem Res 187:163–171. https://doi.org/10.1007/s12011-018-1359-1

    Article  CAS  PubMed  Google Scholar 

  37. Vanhoutte PM, Shimokawa H, Tang EHC, Feletou M (2009) Endothelial dysfunction and vascular disease. Acta Physiol 196:193–222. https://doi.org/10.1111/j.1748-1716.2009.01964.x

    Article  CAS  Google Scholar 

  38. Gökalp O, Özdem S, Dönmez S et al (2009) Impairment of endothelium-dependent vasorelaxation in cadmium-hypertensive rats. Toxicol Ind Health 25:447–453. https://doi.org/10.1177/0748233709106822

    Article  CAS  PubMed  Google Scholar 

  39. Félétou M, Köhler R, Vanhoutte PM (2012) Nitric oxide: Orchestrator of endothelium-dependent responses. Ann Med 44:694–716. https://doi.org/10.3109/07853890.2011.585658

    Article  CAS  PubMed  Google Scholar 

  40. Bolotina VM, Najibi S, Palacino JJ et al (1994) Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368:850–853. https://doi.org/10.1038/368850a0

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Financing code 001); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq—307742/2021–0) and Fundação de Amparo à Pesquisa do Espírito Santo (FAPES –EDITAL PRONEM 20/2022). The funders had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

Authors

Contributions

Data collection and analysis were performed by Karoline Alves Rossi, Camila Cruz Pereira Almenara,. Rakel Passos Simões, Lorraine Christiny Costa Sepulchro Mulher and Maiara. Alessandra Simão Padilha, Camila Cruz Pereira Almenara and Maria Tereza W. D Carneiro were responsible for conceptualization, methodology, and played a significant role in writing, review, and editing of the manuscript. All authors wrote and revised the manuscript.

Corresponding author

Correspondence to Alessandra Simão Padilha.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical Approval

The research protocols performed in this study were in accordance with the guidelines recommended by the Brazilian National Biosafety Commission (CTNBio), Brazilian College of Animal Experimentation (COBEA) and American Physiological Society (APS). The project was previously approved by the Ethics Committee on Experimentation and Use of Animals of the Federal University of Espírito Santo (UFES—CEUA 09/2020).

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rossi, K.A., Almenara, C.C.P., Simões, R.P. et al. Short-term Effects of Cadmium Exposure on Blood Pressure and Vascular Function in Wistar Rats. Biol Trace Elem Res 202, 2645–2656 (2024). https://doi.org/10.1007/s12011-023-03851-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-023-03851-5

Keywords

Navigation