Impact of hypercholesterolemia on acidosis-induced coronary microvascular dilation

Hiroki Shioiri, Tatsuya Komaru, Kouichi Sato, Katsuaki Takahashi, Satoru Takeda, Hiroshi Kanatsuka, Jun Watanabe, Kunio Shirato

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11 Citations (Scopus)

Abstract

An increase in coronary flow conductance during acidosis is an important compensatory mechanism in various diseased conditions. On the other hand, hypercholesterolemia causes microvascular dysfunction as well as macrovascular disorders. We investigated the impact of hypercholesterolemia on the coronary microvascular response to acidosis. Coronary arterioles (< 150 μm) isolated from rabbit hearts were cannulated to micropipettes in a vessel chamber and the microvascular responses were observed. After preconstriction was established, the extravascular pH was gradually reduced from 7.4 to 7.0. The effects of glibenclamide, ATP-sensitive K+ (KATP) channel blocker, (1 μM, n = 4) or pertussis toxin (100 ng/mL, n = 7) on the acidosis-induced microvascular responses were examined. In another set of experiments, rabbits were randomly assigned to normal chow (NC group, n = 18) or high cholesterol (2%) diet (HC group, n = 20). After 8 weeks of feeding, the responses of isolated coronary arterioles to acidosis, ADP, nitroprusside, and levcromakalim were examined in the two groups. Coronary arterioles significantly dilated as the pH was reduced and the dilation was significantly inhibited by glibenclamide or pertussis toxin. Acidosis-induced dilation in the HC group was significantly attenuated compared to the NC group (36.5 ± 2.1 % vs 73.7 ± 4.8 % at pH = 7.0 P < 0.05). There were no significant differences in the dilations by ADP, nitroprusside and levcromakalim between the two groups. In conclusion, acidosis-induced dilation of rabbit coronary arterioles is mediated by the activation of the pertussis toxin-sensitive G protein and KATP channels, and the dilation of coronary arterioles is impaired in hypercholesterolemia. The impairment occurs upstream of KATP channel opening.

Original languageEnglish
Pages (from-to)76-83
Number of pages8
JournalBasic Research in Cardiology
Volume98
Issue number2
DOIs
Publication statusPublished - 2003 Mar 1

Keywords

  • Acidosis
  • Cholesterol
  • Coronary circulation
  • Dilation
  • Microcirculation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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  • Cite this

    Shioiri, H., Komaru, T., Sato, K., Takahashi, K., Takeda, S., Kanatsuka, H., Watanabe, J., & Shirato, K. (2003). Impact of hypercholesterolemia on acidosis-induced coronary microvascular dilation. Basic Research in Cardiology, 98(2), 76-83. https://doi.org/10.1007/s00395-003-0391-1