ANGIOTENSIN-II INHIBITION OF ATP-SENSITIVE K-MUSCLE CELLS THROUGH PROTEIN-KINASE-C( CURRENTS IN RAT ARTERIAL SMOOTH)

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 iso lated enzymatically from rat mesenteric arteries were investigated usi ng the patch clamp technique. 2. Ang II, at a physiological concentrat ion (100 nM), reduced I-K,I-ATP activated by 0.1 mM internal ATP and 1 0 mu M levcromakalim by 36.4 +/- 2.3%. 3. The protein kinase C (PKC) a ctivator 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 ca lphostin C (500 nM) prevented the Ang II-induced inhibition of I-K,I-A TP. 5. Ang II inhibition was unaffected by cell dialysis with PRA inhi bitor 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-A TP channels through activation of PKC but not through inhibition of PK A.