Skip to main content
Log in

Modulation of Pb(II) Caused Aortal Constriction by Eugenol and Carvacrol

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

Abstract

Exposure to lead is known to cause vasoconstriction, exact mechanism of which remains to be elucidated. In this study, we investigate contractile responses of rat aortal rings equilibrated with Pb(II) in organ bath system, explore pathways responsible for hypercontraction and examine two ameliorators of lead-induced hypercontraction. At 1 μmol L−1 Pb(II), aortal rings showed an average increase of 50 % in isometric contraction. Incubation of rings, unexposed to Pb(II), with 1 μmol L−1 sodium nitroprusside (nitric oxide (NO) donor), 100 μmol L−1 apocynin (reactive oxygen species (ROS) inhibitor), and 100 μmol L−1 indomethacin (cyclooxygenase inhibitor) lead to decrease in phenylephrine-induced contraction by 31, 27, and 29 %, respectively. This decrease of contraction for Pb(II)-exposed rings was 48, 53, and 38 %, respectively, indicating that ROS- and NO-dependent components of contractions are significantly elevated in Pb(II)-induced hypercontraction. Cyclooxygenase-dependent contractile component did not show significant elevation. Eugenol and carvacrol are plant-derived phenols known to possess antioxidant activity and hence could act as possible ameliorators of hypercontraction. At saturating concentrations of 100 μmol L−1, eugenol and carvacrol caused a decrease in contraction by 38 and 42 % in unexposed rings and 46 and 50 % in Pb(II)-exposed rings. Co-incubation of rings with eugenol/carvacrol and various inhibitors suggests that both these active principles exert their relaxant effect via quenching of ROS and stimulation of NO synthesis. To conclude, Pb(II) is shown to induce hypercontraction of aortal rings through elevation of ROS and depletion of NO. This hypercontraction is effectively mitigated by eugenol and carvacrol.

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

Similar content being viewed by others

References

  1. Haynes JM, Pennefather JN (1993) A1- and A2-purinoceptors in the guinea-pig uterus. Clin Exp Pharmacol Physiol 20:609–617

    Article  PubMed  CAS  Google Scholar 

  2. Silveira EA, Lizardo JHF, Souza LP, Stefanon I, Vassallo DV (2010) Acute lead-induced vasoconstriction in the vascular beds of isolated perfused rat tails is endothelium-dependent. Braz J Med Biol Res 43(5):492–499

    Article  PubMed  CAS  Google Scholar 

  3. Birder LA, Apodaca G, De Groat WC, Kanai AJ (1998) Adrenergic-and capsaicin-evoked nitric oxide release from urothelium and afferent nerves in urinary bladder. Am J Physiol Renal Physiol 275:F226–F229

  4. Ruan YC, Wang Z, Du JY, Zuo WL, Guo JH, Zhang J, Wu ZL, Wong HY, Chung YW, Chan HC, Zhou WL (2008) Regulation of smooth muscle contractility by the epithelium in rat vas deferens: role of ATP induced release of PGE2. J Physiol 586:4843–4857

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Kopp SJ, Barron JT, Tow JP (1988) Cardiovascular actions of lead and relationship to hypertension: a review. Environ Health Persp 78:91–99

    Article  CAS  Google Scholar 

  6. Vaziri ND, Wang XQ (1999) cGMP-mediated negative-feedback regulation of endothelial nitric oxide synthase expression by nitric oxide. Hypertension 34:1237–1241

    Article  PubMed  CAS  Google Scholar 

  7. Barbosa F, Sertorio JTC, Gerlach RF, Jose E (2006) Clinical evidence for lead-induced inhibition of nitric oxide formation. Arch Toxicol 80:811–816

    Article  PubMed  CAS  Google Scholar 

  8. Schober SE, Mirel LB, Graubard BI, Brody DJ, Flegal KM (2006) Blood lead levels and death from all causes, cardiovascular disease, and cancer: results from the NHANES III Mortality Study. Environ Health Persp 114:1538–1541

    CAS  Google Scholar 

  9. Zhang LF, Peng SQ, Wang S (2005) Influence of lead on reactions of in vitro cultured rat aorta to 5-hydroxytryptamine. Toxicl Lett 159:71–82

    Article  CAS  Google Scholar 

  10. Vaziri ND, Ding Y (2001) Effect of lead on nitric oxide synthase expression in coronary endothelial cells: role of superoxide. Hypertension 37:223–226

    Article  PubMed  CAS  Google Scholar 

  11. Shabir H, Kundu S, Basir SF, Khan LA (2014) Amelioration of lead and cadmium induced rat tracheal hyper-contraction by linalool and eugenol. Toxicol Environ Chem. doi:10.1080/02772248.2014.931520

    Google Scholar 

  12. Vaziri ND (2008) Mechanisms of lead-induced hypertension and cardiovascular disease. Review. Am J Physiol Heart Circ Physiol 295:H454–H465

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Vaziri ND, Lin CY, Farmand F, Sindhu RK (2003) Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension. Kidney Int 63:186–194

    Article  PubMed  CAS  Google Scholar 

  14. Courtois E, Marques M, Barrientos A, Casado S, Lopez-Farre A (2003) Lead induced downregulation of soluble guanylate cyclase in isolated rat aortic segments mediated by reactive oxygen species and cyclooxygenase-2. J Am Soc Nephrol 14:1464–1470

    Article  PubMed  CAS  Google Scholar 

  15. Martinez-Revelles S, Avendano MS, Garcia-Redondo AB, Alvarez Y, Aguado A, Perez-Giron JV, Garcia-Redondo L et al (2013) Reciprocal relationship between reactive oxygen species and cyclooxygenase-2 and vascular dysfunction in hypertension. Antioxid Redox Signal 18:51–65

    Article  PubMed  CAS  Google Scholar 

  16. Nemsadze K, Sanikidze T, Ratiani L, Gabunia L, Sharashenidze T (2009) Mechanisms of lead-induced poisoning. Georgian Med News 172–173:92–96

    PubMed  Google Scholar 

  17. Proestos C, Boziaris IS, Nychas GJE, Komaitis M (2006) Analysis of flavonoids and phenolic acids in Greek aromatic plants: investigation of their antioxidant capacity and antimicrobial activity. Food Chem 95:664–671

    Article  CAS  Google Scholar 

  18. Peixoto-Neves D, Silva-Alves KS, Gomes MD, Lima FC, Lahlou S, Magalhães PJ, Ceccatto VM, Coelho-De-Souza AN, Leal-Cardoso JH (2010) Vasorelaxant effects of the monoterpenic phenol isomers, carvacrol and thymol, on rat isolated aorta. Fundam Clin Pharmacol 24:341–350

    Article  PubMed  CAS  Google Scholar 

  19. Leal-Cardoso JH, Lahlou S, Coelho-de-Souza AN et al (2002) Inhibitory actions of eugenol on rats isolated ileum. Can J Physiol Pharmacol 80:901–906

    Article  PubMed  CAS  Google Scholar 

  20. Damiani CE, Rossoni LV, Vassallo DV (2003) Vasorelaxant effects of eugenol on rat thoracic aorta. Vascul Pharmacol 40:59–66

    Article  PubMed  CAS  Google Scholar 

  21. Lima FC, Peixoto-Neves D, Gomes MDM, Coelho-de-Souza AN, Lima CC, Araújo Zin W, Magalhães PJC, Saad L, Leal-Cardoso JH (2011) Antispasmodic effects of eugenol on rat airway smooth muscle. Fund Clinic Pharmacol 25:690–699

    Article  CAS  Google Scholar 

  22. Criddle DN, Madeira SV, Soares de Moura R (2003) Endothelium-dependent and independent vasodilator effects of eugenol in the rat mesenteric vascular bed. J Pharm Pharmacol 55:359–365

    Article  PubMed  CAS  Google Scholar 

  23. Lahlou S, Interaminense LFL, Magalhães PJC, Leal-Cardoso JH, Duarte GP (2004) Cardiovascular effects of eugenol, a phenolic compound present in many plant essential oils in normotensive rats. J Cardiovasc Pharmacol 43:250–257

    Article  PubMed  CAS  Google Scholar 

  24. Trailovic MS, Robertson PA, Jelena NT (2009) Inhibitory effect of eugenol on rat ileal motility in vitro. Acta Veterinaria 59:123–131

    Article  Google Scholar 

  25. Ogata M, Hoshi M, Urano S, Endo T (2000) Antioxidant activity of eugenol and related monomeric and dimeric compounds. Chem Pharm Bull 48:1467–1469

    Article  PubMed  CAS  Google Scholar 

  26. Earley S, Gonzales AL, Garcia ZI (2010) A dietary agonist of transient receptor potential cation channel V3 elicits endothelium-dependent vasodilation. Mol Pharmacol 77:612–620

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Oliveira, da Silva FV, Viana AFSC, Martins MDCC, Nunes PHM, Oliveira FDA, Oliveira RDCM (2012) Gastroprotective activity of carvacrol on experimentally induced gastric lesions in rodents. Naunyn-Schmiedeberg’s Arch Pharmacol 385:899–908

    Article  CAS  Google Scholar 

  28. Guimaraes AG, Oliveira GF, Melo MS, Cavalcanti SC, Antoniolli AR, Bonjardim LR, Silva FA, Santos JP, Rocha RF, Moreira JC, Araujo AA, Gelain DP, Qunitans LJ Jr (2010) Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Basic Clin Pharmacol Toxicol 107:949–957

    Article  PubMed  CAS  Google Scholar 

  29. Sticht F, Smith RM (1971) Eugenol: some pharmacologic observations. J Dent Res 50:1531–1535

    Article  PubMed  CAS  Google Scholar 

  30. Aydin Y, Kutlay O, Ari S, Duman S, Uzuner K, Aydin S (2007) Hypotensive effects of carvacrol on the blood pressure of normotensive rats. Planta Med 73(13):1365–1371

    Article  PubMed  CAS  Google Scholar 

  31. Ansari HR, Nadeem A, Talukder MAH, Sakhalkar S, Mustafa SJ (2007) Evidence for the involvement of nitric oxide in A2B receptor-mediated vasorelaxation of mouse aorta. Am J Physiol Heart Circ Physiol 292:719–725

    Article  Google Scholar 

  32. Wallerstedt SM, Bodolsson M (1997) Effect of propofol on isolated human omental arteries and veins. Br J Anaesth 78:296–300

    Article  PubMed  CAS  Google Scholar 

  33. Teng B, Qin W, Ansari HR, Mustafa SJ (2005) Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery. Am J Physiol Heart Circ Physiol 288:H2574–H2580

    Article  PubMed  CAS  Google Scholar 

  34. Khalil RA, Crews JK, Novak J, Kassab S, Granger JP (1998) Enhanced vascular reactivity during inhibition of nitric oxide synthesis in pregnant rats. Hypertension 31:1065–1069

    Article  PubMed  CAS  Google Scholar 

  35. Fazli-Tabaei S, Fahim M (2006) Khoshbaten A (2006) Acute lead exposure and contraction of rat isolated aorta induced by D1-dopaminergic and alpha-adrenergic drugs. Arch Iran Med 9(2):119–123

    PubMed  CAS  Google Scholar 

  36. Agency for toxic substances and disease registry (2007) Toxicological profile for lead. U.S Department of Health and Human Services

  37. Centers for Disease Control and Prevention (2014) Lead. 1600 Clifton Rd. Atlanta, GA 30333, USA. http://www.cdc.gov/nceh/lead/. Accessed 19 June 2014

  38. Khalil-Manesh F, Gonick HC, Weiler EW, Prins B, Weber MA, Purdy R (1993) Lead-induced hypertension: possible role of endothelial factors. Am J Hypertens 6:723–729

    PubMed  CAS  Google Scholar 

  39. Shelkovnikov SA, Gonick HC (2001) Influence of lead on rat thoracic aorta contraction and relaxation. Am J Hypertens 14:873–878

    Article  PubMed  CAS  Google Scholar 

  40. Watts SW, Chai S, Webb RC (1995) Lead acetate-induced contraction in rabbit mesenteric artery: interaction with calcium and protein kinase C. Toxicology 99:55–65

    Article  PubMed  CAS  Google Scholar 

  41. Webb RC, Winquist RJ, Victery W, Wander AJ (1981) In vivo and in vitro effects of lead on vascular reactivity in rats. Am J Physiol 241:H211–H216

    PubMed  CAS  Google Scholar 

  42. Jin N, Packer CS, Rhoades RA (1991) Reactive oxygen-mediated contraction in pulmonary arterial smooth muscle: cellular mechanisms. Can J Physiol Pharmacol 69:383–388

    Article  PubMed  CAS  Google Scholar 

  43. Rauan YC, Zhou W, Chan HC (2011) Regulation of smooth muscle contraction by the epithelium: role of prostaglandins. Physiology 26:156–170

    Article  Google Scholar 

  44. Sausbier M, Schubert R, Voigt V, Hirneiwss C, Pfeifer A, Korth M (2000) Mechanisms of NO/cGMP dependent vasorelaxation. Circ Res 87:825–830

    Article  PubMed  CAS  Google Scholar 

  45. Nagababu E, Rifkind JM, Boindala S, Nakka L (2001) Assessment of anti oxidant activities of Eugenol by in vitro and in vivo methods. Methods Mol Biol 610:165–180

    Article  Google Scholar 

  46. Guimarães AG, Oliveira GF, Melo MS, Cavalcanti SC, Antoniolli AR, Bonjardim LR et al (2010) Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol. Bas Clin Pharmacol Toxicol 107:949–957

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by funding from UGC (SAP) DRS-I (F.3-20/2011) to Prof. SFB and Prof. LAK.

Conflict of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Luqman A. Khan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shabir, H., Kundu, S., Basir, S.F. et al. Modulation of Pb(II) Caused Aortal Constriction by Eugenol and Carvacrol. Biol Trace Elem Res 161, 116–122 (2014). https://doi.org/10.1007/s12011-014-0081-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0081-x

Keywords

Navigation