Influence of endothelium in contraction induced by phorbol ester in isolated rat aortic rings.
The present study aimed to investigate the possible role of endothelium in contractile response to phorbol 12,13-diacetate (PDA) by measuring the contractile force in rat isolated aortic rings. PDA at low concentrations induced small and sustained tension in arteries with intact endothelium. N(G)-Nitro-L-arginine (100 microM), a nitric oxide synthase inhibitor and methylene blue (10 microM), an O2-generator induced a large increase in tension in the presence of PDA. The magnitude of contractions in response to N(G)-Nitro-L-arginine was related to concentrations of PDA. Staurosporine (10 nM), an inhibitor of protein kinase C completely inhibited contractile response to PDA as well as potentiating effects of N(G)-Nitro-L-arginine and methylene blue. Removal of the endothelium abolished contractile responses to both N(G)-Nitro-L-arginine and methylene blue in the presence of PDA. Removal of extracellular Ca2+ suppressed contractile responses to both PDA and N(G)-Nitro-L-arginine. On the other hand, N(G)-Nitro-L-arginine (100 microM) did not induce contractions of the rat aorta pre-treated with 4-alpha-phorbol 12-myristate 13-acetate, an inactive form of phorbol ester. Acetylcholine concentration-dependently induced reduction of tension induced by PDA (0.3 microM) in rat aorta. N(G)-Nitro-L-arginine or removal of endothelium prevented the effect of the acetylcholine-induced relaxation. Indomethacin (1 microM), glibenclamide (3 microM) and charybdotoxin (100 nM) did not affect the PDA response in rat aorta. These results indicate that in rat aorta, the basal release of nitric oxide could modulate the PDA-induced contraction, which is likely to accounts for the smaller contractile response induced by PDA in arteries with intact endothelium compared to much larger contractions seen in arteries without endothelium.
Huang
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Y
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010703:Phorbol Esters; C008874:phorbol-12,13-diacetate; D011493:Protein Kinase C; D000109:Acetylcholine; D002118:Calcium