Impaired arachidonic acid-mediated activation of large-conductance Ca 2+-activated K+ channels in coronary arterial smooth muscle cells in Zucker Diabetic Fatty rats

Tong Lu, Xiao Li Wang, Tongrong He, Wei Zhou, Terry L. Kaduce, Zvonimir S. Katusic, Arthur A. Spector, Hon Chi Lee

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

We studied the arachidonic acid (AA)-mediated modulation of large-conductance Ca2+-activated K+ (BK) channels in coronary arterial smooth myocytes from lean control and Zucker Diabetic Fatty (ZDF) rats. A total of 1 μmol/l AA enhanced BK current by 274% in lean and by 98% in ZDF rats. After incubation with 10 μmol/l indomethacin, 1 μmol/l AA increased BK currents by 80% in lean and by 70% in ZDF rats. Vasoreactivity studies showed that the dilation of small coronary arteries produced by 1 μmol/l AA was reduced by 44% in ZDF rats. [3H]6-keto-prostagladin F ([3H]6-keto-PGF,), the stable metabolite of prostacyclin (PGI2), was the major [3H]AA metabolite produced by coronary arteries of lean vessels, but ZDF vessels produced only 15% as much [3H]6-keto-PGF. BK channel activation and vasorelaxation by iloprost were similar in lean and ZDF rats. Immunoblots showed a 73% reduction in PGI2 synthase (PGIS) expression in ZDF vessels compared with lean vessels, and there was no change in cyclooxygenase (COX) and BK channel expressions. Real-time PCR studies showed that mRNA levels of PGIS, COX-1, and COX-2 were similar between lean and ZDF vessels. We conclude that PGI2 is the major AA metabolite in lean coronaries, and AA-mediated BK channel activation is impaired in ZDF coronaries due to reduced PGIS activity.

Original languageEnglish (US)
Pages (from-to)2155-2163
Number of pages9
JournalDiabetes
Volume54
Issue number7
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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