Endothelium-derived relaxing factor inhibits the endothelin-1-induced increase in protein kinase C activity in rat aorta.
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.
Lang
D
D
Department of Pharmacology & Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff.
Lewis
M J
MJ
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D016232:Endothelins; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D000001:Calcimycin; D009320:Atrial Natriuretic Factor; D001120:Arginine; D011493:Protein Kinase C