Angiotensin II Inhibition of ATP-Sensitive K+ Currents in Rat Arterial Smooth Muscle Cells Through Protein Kinase C

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Abstract

  • 1The effects of the vasoconstrictor angiotensin II (Ang II) on whole-cell ATP-sensitive K+currents (Ik,atp) of smooth muscle cells isolated enzymatically from rat mesenteric arteries were investigated using the patch clamp technique.
  • 2Ang II, at a physiological concentration (100 nm), reduced Ik,atp activated by 0.1 mm internal ATP and 10 μm levcromakalim by 36.4 ± 2.3%.
  • 3The protein kinase C (PKC) activator 1-oleoyl-2-acetyl-sn-glycerol (OAG, 1 μm) reduced Ik,atp by 44.1 ± 2.7%. GDPβS (1 mm), included in the pipette solution, abolished the inhibition by Ang II, while that by OAG was unaffected.
  • 4Pretreatment with the PKC inhibitors staurosporine (100 nm) or calphostin C (500 nm) prevented the Ang II-induced inhibition of Ik,atp.
  • 5Ang II inhibition was unaffected by cell dialysis with PKA inhibitor peptide (5 μm), and the PKA inhibitor Rp-cAMPS (100 μ) did not reduce Ik,atp.
  • 6Our results suggest that Ang II modulates Katp channels through activation of PKC but not through inhibition of PKA.

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