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(Circulation Research. 2001;89:174.)
© 2001 American Heart Association, Inc.

Integrative Physiology

Impaired Hyperpolarization in Regenerated Endothelium After Balloon Catheter Injury

Ralf Köhler, Susanne Brakemeier, Meike Kühn, Claudia Behrens, Robert Real, Christiane Degenhardt, Hans-Dieter Orzechowski, Axel R. Pries, Martin Paul, Joachim Hoyer

From the Departments of Nephrology (R.K., S.B., M.K., C.B., C.D., J.H.) and Clinical Pharmacology (R.R., H.-D.O., M.P.), Benjamin Franklin Medical Center, and the Institute for Physiology (A.R.P.), Freie Universität, Berlin, Germany.

Correspondence to R. Köhler, Benjamin Franklin Medical Center, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail koe{at}zedat.fu-berlin.de

Abstract— Ca²⁺-activated K⁺ (K_Ca) channels control endothelial Ca²⁺ homeostasis and the formation of vasodilators. After angioplasty, dysfunction of the regenerated endothelium leads to abnormal vasoregulation. In this study, we tested the expression and function of K_Ca channels in regenerated endothelium at 6 weeks after balloon catheter injury of rat carotid arteries (CAs) by using single-cell reverse transcription–polymerase chain reaction, patch-clamp techniques, and analysis of vasoreactivity. In single regenerated endothelial cells (ECs), the percentage of ECs expressing the K_Ca genes, rSK3 (12±8%) and rIK1 (22±9%), was significantly lower compared with the percentage of native ECs expressing these genes (rSK3 58±8%, rIK1 64±10%). In patch-clamp experiments, K_Ca currents and acetylcholine-induced hyperpolarization were markedly reduced in regenerated ECs (shift of membrane potential -6±3 mV) compared with those in native ECs (shift of membrane potential -21±5 mV). In pressure myograph experiments, acetylcholine-induced dilation was impaired in reendothelialized CAs compared with normal CAs. Intraluminal application of the K_Ca blocker apamin and charybdotoxin inhibited dilation by 30% in normal CAs but was without effect in reendothelialized CAs. Intraluminal application of 1-ethyl-2-benzimidazolinone (100 µmol/L), an opener of K_Ca channels, evoked dilation by 29% in normal CAs but had no effect in reendothelialized CAs. In conclusion, the impaired expression of K_Ca channels in regenerated endothelium results in defective hyperpolarization and impaired dilation. Thus, the impaired K_Ca channel function contributes to functional alterations of regenerated endothelium after angioplasty.

Key Words: angioplasty • neointima • endothelium • Ca²⁺-activated K⁺ channels • endothelium-dependent vasodilation

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