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Species-specific differences in the role of L-type Ca2+ channels in the regulation of coronary arterial smooth muscle contraction

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Abstract

The L-type calcium channel (LCC) plays a regulatory role in various physical and pathological processes. In the vasculature, LCCs mediate agonist-induced vascular smooth muscle contraction. However, whether LCC-mediated vessel responses to certain vasoconstrictors vary among species remains unclear. The coronary arteries were dissected from the hearts of rats and mice. Coronary arterial ring contraction was measured using the Multi Myograph system. High K+ (60 mM)-induced coronary artery contractions were stronger in rats than in mice, whereas CaCl2-induced contraction curves did not differ significantly between the two groups. Endothelin-1, U46619 (thromboxane A2 receptor agonist), and 5-hydroxytryptamine (5-HT) induced concentration-dependent vasoconstriction of coronary arterial rings in rats and mice. The vessel rings of mice were more sensitive to ET-1 and U46619 and less sensitive to 5-HT than those of rats. The LCC blocker nifedipine significantly inhibited coronary artery contractions induced by ET-1, U46619, and 5-HT. The inhibitory effect of 1 μM nifedipine on ET-1- and 5-HT-induced coronary artery contractions was stronger in mice than in rats, whereas its effect on U46619-induced vessel contractions was weaker in mice than in rats. The 5-HT2A receptor and LCC mRNA levels were higher in the coronary arteries of rats than in those of mice, whereas the expressions of the ETA and TXA2 receptors and Orai1 mRNA levels were comparable between the two groups. LCC plays an important role in coronary arterial contraction. Rats and mice show different responses to vasoconstrictors and LCC blockers, suggesting that the coronary arteries of rats and mice have different biological characteristics.

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References

  • Alapati VR, McKenzie C, Blair A, Kenny D, MacDonald A, Shaw AM (2009) Mechanisms of U46619- and 5-HT-induced contraction of bovine pulmonary arteries: role of chloride ions. Br J Pharmacol 151:1224–1234

    Article  Google Scholar 

  • Benitah JP, Alvarez JL, Gomez AM (2010) L-type Ca2+ current in ventricular cardiomyocytes. J Mol Cell Cardiol 48:26–36

    Article  PubMed  CAS  Google Scholar 

  • Bolotina VM (2012) Orai1, STIM1, and iPLA2 determine arterial vasoconstriction. Arterioscler Thromb Vasc Biol 32:1066–1067

    Article  PubMed  CAS  Google Scholar 

  • Dominguez-Rodriguez A, Diaz I, Rodriguez-Moyano M, Calderon-Sanchez E, Rosado JA, Ordonez A, Smani T (2012) Urotensin-II signaling mechanism in rat coronary artery: role of STIM1 and Orai1-dependent store operated calcium influx in vasoconstriction. Arterioscler Thromb Vasc Biol 32:1325–1332

    Article  PubMed  CAS  Google Scholar 

  • Elmoselhi AB, Grover AK (1997) Endothelin contraction in pig coronary artery: receptor types and Ca(2+)-mobilization. Mol Cell Biochem 176:29–33

    Article  PubMed  CAS  Google Scholar 

  • Halcox JP, Nour KR, Zalos G, Quyyumi AA (2001) Coronary vasodilation and improvement in endothelial dysfunction with endothelin ET(A) receptor blockade. Circ Res 89:969–976

    Article  PubMed  CAS  Google Scholar 

  • Halcox JP, Nour KR, Zalos G, Quyyumi AA (2007) Endogenous endothelin in human coronary vascular function: differential contribution of endothelin receptor types A and B. Hypertension 49:1134–1141

    Article  PubMed  CAS  Google Scholar 

  • Higashino R, Sato R, Jin H, Inoue N, Fukuta Y, Kurimoto T, Tamaki H (1997) Inhibitory effects of efonidipine hydrochloride on contraction induced by several vasoconstrictors in porcine coronary artery: comparison with effects of nifedipine and nisoldipine. J Cardiovasc Pharmacol 29:624–630

    Article  PubMed  CAS  Google Scholar 

  • Ito A, Shimokawa H, Nakaike R, Fukai T, Sakata M, Takayanagi T, Egashira K, Takeshita A (1994) Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm in a swine model. Circulation 90:2425–2431

    Article  PubMed  CAS  Google Scholar 

  • Katugampola SD, Davenport AP (2001) Thromboxane receptor density is increased in human cardiovascular disease with evidence for inhibition at therapeutic concentrations by the AT(1) receptor antagonist losartan. Br J Pharmacol 134:1385–1392

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kawanabe Y, Masaki T, Hashimoto N (2006) Involvement of phospholipase C in endothelin 1-induced stimulation of Ca++ channels and basilar artery contraction in rabbits. J Neurosurg 105:288–293

    Article  PubMed  CAS  Google Scholar 

  • Kizub IV, Klymenko KI, Soloviev AI (2014) Protein kinase C in enhanced vascular tone in diabetes mellitus. Int J Cardiol 174:230–242

    Article  PubMed  Google Scholar 

  • Kruse HJ, Bauriedel G, Heimerl J, Hofling B, Weber PC (1994) Role of L-type calcium channels on stimulated calcium influx and on proliferative activity of human coronary smooth muscle cells. J Cardiovasc Pharmacol 24:328–335

    Article  PubMed  CAS  Google Scholar 

  • Kuga T, Shimokawa H, Hirakawa Y, Kadokami Y, Arai Y, Fukumoto Y, Kuwata K, Kozai T, Egashira K, Takeshita A (2000) Increased expression of L-type calcium channels in vascular smooth muscle cells at spastic site in a porcine model of coronary artery spasm. J Cardiovasc Pharmacol 35:822–828

    Article  PubMed  CAS  Google Scholar 

  • Matchkov VV, Kudryavtseva O, Aalkjaer C (2012) Intracellular Ca2+ signalling and phenotype of vascular smooth muscle cells. Basic Clin Pharmacol Toxicol 110:42–48

    Article  PubMed  CAS  Google Scholar 

  • Nichols DE, Nichols CD (2008) Serotonin receptors. Chem Rev 108:1614–1641

    Article  PubMed  CAS  Google Scholar 

  • Salamanca DA, Khalil RA (2005) Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. Biochem Pharmacol 70:1537–1547

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Soboloff J, Rothberg BS, Madesh M, Gill DL (2012) STIM proteins: dynamic calcium signal transducers. Nat Rev Mol Cell Biol 13:549–565

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83:1325–1358

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant numbers 81273516, 81270222, 81302779, and 81470440) and by Guangdong Provincial Natural Science Foundation (S2013010014762 and S2013040014689).

Conflict of interest

The authors declare that they have no competing interests.

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    Authors and Affiliations

    1. Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, 96 Dongchuan Road Weilun Building, Guangzhou, 510080, People’s Republic of China

      Hui Yang, Su-Juan Kuang, Fang Rao, Yu-Mei Xue, Xiao-Ying Liu, Zhi-Xin Shan, Xiao-Hong Li, Jie-Ning Zhu, Zhi-Ling Zhou, Xiao-juan Zhang, Qiu-Xiong Lin, Xi-Yong Yu & Chun-Yu Deng

    2. Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China

      Hui Yang, Su-Juan Kuang, Fang Rao, Yu-Mei Xue, Xiao-Ying Liu, Zhi-Xin Shan, Xiao-Hong Li, Jie-Ning Zhu, Zhi-Ling Zhou, Qiu-Xiong Lin, Xi-Yong Yu & Chun-Yu Deng

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    1. Hui Yang
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    Correspondence to Xi-Yong Yu or Chun-Yu Deng.

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    Hui Yang and Su-Juan Kuang contributed equally to this work.

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    Yang, H., Kuang, SJ., Rao, F. et al. Species-specific differences in the role of L-type Ca2+ channels in the regulation of coronary arterial smooth muscle contraction. Naunyn-Schmiedeberg's Arch Pharmacol 389, 151–157 (2016). https://doi.org/10.1007/s00210-015-1173-7

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