Endothelium-derived relaxing factor inhibits the endothelin-1-induced increase in protein kinase C activity in rat...

1. Particulate and cytosolic protein kinase C (PKC) activity was measured in rat aortae with and without endothelium, following exposure to endothelin-1 (10(-8) M) for various time intervals. 2. Endothelin-1 induced two peaks of particulate PKC activity, occurring at 30 s and 10 min exposure times in both endothelium-intact and endothelium-denuded preparations. Cytosolic PKC activity fell below baseline at all incubation times studied. 3. In endothelium-denuded preparations, elevation of guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels with sodium nitroprusside (10(-6) M) or atrial natriuretic peptide (10(-6) M) and, in endothelium-intact preparations with the calcium ionophore A23187 (10(-6) M), inhibited the activation of particulate PKC activity seen after incubation with endothelin-1 for 30 s. The inhibitory effect of A23187 was prevented by prior incubation of the endothelium-intact vessels with the nitric oxide synthetase inhibitor, L-NG-nitro arginine (5 x 10(-5) M). 4. These results indicate that EDRF acting via cyclic GMP can inhibit the activation of PKC induced by endothelin-1 in rat aorta.