Angiotensin II inhibition of ATP-sensitive K+ currents in rat arterial smooth muscle cells through protein kinase C

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