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Low K+ current in arterial myocytes with impaired K+-vasodilation and its recovery by exercise in hypertensive rats

  • Ion channels, receptors and transporters
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Abstract

K+ channels determine the plasma membrane potential of vascular myocytes, influencing arterial tone. In many types of arteries, a moderate increase in [K+]e induces vasorelaxation by augmenting the inwardly rectifying K+ channel current (I Kir). K+-vasodilation matches regional tissue activity and O2 supply. In chronic hypertension (HT), small arteries and arterioles undergo various changes; however, ion channel remodeling is poorly understood. Here, we investigated whether K+ channels and K+-induced vasodilation are affected in deep femoral (DFA) and cerebral artery (CA) myocytes of angiotensin II-induced hypertensive rats (Ang-HT). Additionally, we tested whether regular exercise training (ET) restores HT-associated changes in K+ channel activity. In Ang-HT, both the voltage-gated K+ channel current (I Kv) and I Kir were decreased in DFA and CA myocytes, and were effectively restored and further increased by combined ET for 2 weeks (HT-ET). Consistently, K+-vasodilation of the DFA was impaired in Ang-HT, and recovered in HT-ET. Interestingly, ET did not reverse the decreased K+-vasodilation of CA. CA myocytes from the Ang-HT and HT-ET groups demonstrated, apart from K+ channel changes, an increase in nonselective cationic current (I NSC). In contrast, DFA myocytes exhibited decreased I NSC in both the Ang-HT and HT-ET groups. Taken together, the decreased K+ conductance in Ang-HT rats and its recovery by ET suggest increased peripheral arterial resistance in HT and the anti-hypertensive effects of ET, respectively. In addition, the common upregulation of I NSC in the CA in the Ang-HT and HT-ET groups might imply a protective adaptation preventing excessive cerebral blood flow under HT and strenuous exercise.

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Abbreviations

HT:

Hypertension

Ang II:

Angiotensin II

ET:

Exercise training

Kir:

Inwardly rectifying K+ channel

Kv:

Voltage-gated K+ channel

NSC:

Nonselective cation channel

TPR:

Total peripheral resistance

DFA:

Deep femoral artery

CA:

Cerebral artery

SMC:

Smooth muscle cell

References

  1. Albert AP, Saleh SN, Large WA (2009) Identification of canonical transient receptor potential (TRPC) channel proteins in native vascular smooth muscle cells. Curr Med Chem 16:1158–1165

    Article  PubMed  CAS  Google Scholar 

  2. Amberg GC, Santana LF (2003) Downregulation of the BK channel beta1 subunit in genetic hypertension. Circ Res 93:965–971

    Article  PubMed  CAS  Google Scholar 

  3. Amberg GC, Santana LF (2006) Kv2 channels oppose myogenic constriction of rat cerebral arteries. Am J Physiol Cell Physiol 291:C348–C356

    Article  PubMed  CAS  Google Scholar 

  4. Bae YM, Kim A, Lee YJ, Lim W, Noh YH, Kim EJ, Kim J, Kim TK, Park SW, Kim B, Cho SI, Kim DK, Ho WK (2007) Enhancement of receptor-operated cation current and TRPC6 expression in arterial smooth muscle cells of deoxycorticosterone acetate-salt hypertensive rats. J Hypertens 25:809–817

    Article  PubMed  CAS  Google Scholar 

  5. Bastide M, Ouk T, Pétrault O, Bordet R (2013) Time-induced progressive alteration of Kir current in cerebral smooth muscle cells of stroke-prone spontaneously hypertensive rats. Int J Hypertens. doi:10.1155/2013/849750, Published online April 23

    PubMed  PubMed Central  Google Scholar 

  6. Bertoldi D, Parzy E, Fromes Y, Wary C, Leroy-Willig A, Carlier PG (2006) New insight into abnormal muscle vasodilatory responses in aged hypertensive rats by in vivo nuclear magnetic resonance imaging of perfusion. J Vasc Res 43:149–156

    Article  PubMed  Google Scholar 

  7. Cho YE, Ahn DS, Morgan KG, Lee YH (2011) Enhanced contractility and myosin phosphorylation induced by Ca2+-independent MLCK activity in hypertensive rats. Cardiovasc Res 91:162–170

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. De Clerck I, Boussery K, Pannier JL, Van De Voorde J (2003) Potassium potently relaxes small rat skeletal muscle arteries. Med Sci Sports Exerc 35:2005–2012

    Article  PubMed  Google Scholar 

  9. Fujii K, Tominaga M, Ohmori S, Kobayashi K, Koga T, Takata Y, Fujishima M (1992) Decreased endothelium-dependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats. Circ Res 70:660–669

    Article  PubMed  CAS  Google Scholar 

  10. Giles TD, Sander GE, Nossaman BD, Kadowitz PJ (2012) Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins. J Clin Hypertens (Greenwich) 14:198–205

    Article  CAS  Google Scholar 

  11. Goto K, Rummery NM, Grayson TH, Hill CE (2004) Attenuation of conducted vasodilatation in rat mesenteric arteries during hypertension: role of inwardly rectifying potassium channels. J Physiol Lond 561:215–231

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Gündüz F, Koçer G, Ulker S, Meiselman HJ, Başkurt OK, Sentürk UK (2011) Exercise training enhances flow-mediated dilation in spontaneously hypertensive rats. Physiol Res 60:589–597

    PubMed  Google Scholar 

  13. Hellsten Y, Jensen L, Thaning P, Nyberg M, Mortensen S (2012) Impaired formation of vasodilators in peripheral tissue in essential hypertension is normalized by exercise training: role of adenosine and prostacyclin. J Hypertens 30:2007–2014

    Article  PubMed  CAS  Google Scholar 

  14. Horta PP, de Carvalho JJ, Mandarim-de-Lacerda CA (2005) Exercise training attenuates blood pressure elevation and adverse remodeling in the aorta of spontaneously hypertensive rats. Life Sci 77:3336–3343

    Article  PubMed  CAS  Google Scholar 

  15. Hughes JM, Bund SJ (2002) Arterial myogenic properties of the spontaneously hypertensive rat. Exp Physiol 87:527–534

    Article  PubMed  Google Scholar 

  16. Jackson DN, Moore AW, Segal SS (2010) Blunting of rapid onset vasodilatation and blood flow restriction in arterioles of exercising skeletal muscle with aging in male mice. J Physiol Lond 12:2269–2282

    Article  Google Scholar 

  17. Jin CZ, Jang JH, Kim HJ, Wang Y, Hwang IC, Sadayappan S, Park BM, Kim SH, Jin ZH, Seo EY, Kim KH, Kim YJ, Kim SJ, Zhang YH (2013) Myofilament Ca2+ desensitization mediates positive lusitropic effect of neuronal nitric oxide synthase in left ventricular myocytes from murine hypertensive heart. J Mol Cell Cardiol 60:107–115

    Article  PubMed  CAS  Google Scholar 

  18. Jin CZ, Kim HS, Seo EY, Shin DH, Park KS, Chun YS, Zhang YH, Kim SJ (2011) Exercise training increases inwardly rectifying K+ current and augments K+ mediated vasodilatation in deep femoral artery of rats. Cardiovasc Res 91:142–150

    Article  PubMed  CAS  Google Scholar 

  19. Jordão MT, Ladd FV, Coppi AA, Chopard RP, Michelini LC (2011) Exercise training restores hypertension-induced changes in the elastic tissue of the thoracic aorta. J Vasc Res 48:513–524

    Article  PubMed  Google Scholar 

  20. Joseph BK, Thakali KM, Moore CL, Rhee SW (2013) Ion channel remodeling in vascular smooth muscle during hypertension: Implications for novel therapeutic approaches. Pharmacol Res 70:126–138

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Kharade SV, Sonkusare SK, Srivastava AK, Thakali KM, Fletcher TW, Rhee SW, Rusch NJ (2013) The β3 subunit contributes to vascular calcium channel upregulation and hypertension in angiotensin II-infused C57BL/6 mice. Hypertension 61:137–142

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Liu D, Yang D, He H, Chen X, Cao T, Feng X, Ma L, Luo Z, Wang L, Yan Z, Zhu Z, Tepel M (2009) Increased transient receptor potential canonical type 3 channels in vasculature from hypertensive rats. Hypertension 53:70–76

    Article  PubMed  CAS  Google Scholar 

  23. Liu Y, Pleyte K, Knaus HG, Rusch NJ (1997) Increased expression of Ca2+-sensitive K+ channels in aorta of hypertensive rats. Hypertension 30:1403–1409

    Article  PubMed  CAS  Google Scholar 

  24. Merkus D, Sorop O, Houweling B, Hoogteijling BA, Duncker DJ (2006) KCa channels contribute to exercise-induced coronary vasodilation in swine. Am J Physiol Heart Circ Physiol 291:H2090–H2097

    Article  PubMed  CAS  Google Scholar 

  25. Nakahata K, Kinoshita H, Tokinaga Y, Ishida Y, Kimoto Y, Dojo M, Mizumoto K, Ogawa K, Hatano Y (2006) Vasodilation mediated by inward rectifier K+ channels in cerebral microvessels of hypertensive and normotensive rats. Anesth Analg 102:571–576

    Article  PubMed  CAS  Google Scholar 

  26. Nelson MT, Quayle JM (1995) Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 268:C799–C822

    PubMed  CAS  Google Scholar 

  27. Padilla J, Simmons GH, Bender SB, Arce-Esquivel AA, Whyte JJ, Laughlin MH (2011) Vascular effects of exercise: endothelial adaptations beyond active muscle beds. Physiology (Bethesda) 26:132–145

    Article  Google Scholar 

  28. Park WS, Han J, Earm YE (2008) Physiological role of inward rectifier K+ channels in vascular smooth muscle cells. Pflugers Arch 457:137–147

    Article  PubMed  CAS  Google Scholar 

  29. Pesic A, Madden JA, Pesic M, Rusch NJ (2004) High blood pressure upregulates arterial L-type Ca2+ channels: is membrane depolarization the signal? Circ Res 94:e97–e104

    Article  PubMed  CAS  Google Scholar 

  30. Plant TD, Schaefer M (2005) Receptor-operated cation channels formed by TRPC4 and TRPC5. Naunyn Schmiedebergs Arch Pharmacol 371:266–276

    Article  PubMed  CAS  Google Scholar 

  31. Sarelius I, Pohl U (2010) Control of muscle blood flow during exercise: local factors and integrative mechanisms. Acta Physiol (Oxf) 199:349–365

    Article  CAS  Google Scholar 

  32. Schulte KL, Braun J, Meyer-Sabellek W, Wegscheider K, Gotzen R, Distler A (1988) Functional versus structural changes of forearm vascular resistance in hypertension. Hypertension 11:320–325

    Article  PubMed  CAS  Google Scholar 

  33. Shi L, Liu B, Li N, Xue Z, Liu X (2013) Aerobic exercise increases BK(Ca) channel contribution to regulation of mesenteric arterial tone by upregulating β1-subunit. Exp Physiol 98:326–336

    Article  PubMed  CAS  Google Scholar 

  34. Silverthorn DU, Ober WC, Garrison CW, Silverthorn AC, Johnson BR (2007) Human physiology: an integrated approach, 4th edn. Pearson, pp 514–515 (chapter 15)

  35. Smith PD, Brett SE, Luykenaar KD, Sandow SL, Marrelli SP, Vigmond EJ, Welsh DG (2008) KIR channels function as electrical amplifiers in rat vascular smooth muscle. J Physiol Lond 586:1147–1160

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  36. Tajada S, Cidad P, Moreno-Domínguez A, Pérez-García MT, López-López JR (2012) High blood pressure associates with the remodeling of inward rectifier K+ channels in mice mesenteric vascular smooth muscle cells. J Physiol Lond 590:6075–6091

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Trott DW, Gunduz F, Laughlin MH, Woodman CR (2009) Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries. J Appl Physiol 106:1925–1934

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Watanabe H, Murakami M, Ohba T, Takahashi Y, Ito H (2008) TRP channel and cardiovascular disease. Pharmacol Ther 118:337–351

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (NRF 2011-0017370 and NRF 2012-0000809).

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Authors and Affiliations

  1. Department of Physiology, Department of Biomedical Sciences, and Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Daehak-Ro 103, Jongro-Gu, Seoul, 110-799, South Korea

    Eun Yeong Seo, Hae Jin Kim, Zai Hao Zhao, Ji Hyun Jang, Chun Zi Jin, Yin-Hua Zhang & Sung Joon Kim

  2. Chung-Ang University College of Nursing, Seoul, 100-031, South Korea

    Hae Young Yoo

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  1. Eun Yeong Seo
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Correspondence to Sung Joon Kim.

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Seo, E.Y., Kim, H.J., Zhao, Z.H. et al. Low K+ current in arterial myocytes with impaired K+-vasodilation and its recovery by exercise in hypertensive rats. Pflugers Arch - Eur J Physiol 466, 2101–2111 (2014). https://doi.org/10.1007/s00424-014-1473-7

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  • DOI: https://doi.org/10.1007/s00424-014-1473-7

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