2004年2月
Role of PKC in the attenuation of the cGMP-mediated relaxation of skinned resistance artery smooth muscle seen in glyceryl-trinitrate-tolerant rabbit
BRITISH JOURNAL OF PHARMACOLOGY
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- 巻
- 141
- 号
- 3
- 開始ページ
- 391
- 終了ページ
- 398
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/sj.bjp.0705625
- 出版者・発行元
- NATURE PUBLISHING GROUP
I We examined whether 10 days' in vivo treatment with glyceryl trinitrate (GTN) might reduce cGMP-induced relaxation in the smooth muscle of rabbit mesenteric resistance arteries and, if so, whether protein kinase C (PKC) plays a role in this downregulation.
2 The relaxation responses to GTN and the nitric oxide donor NOC-7 were significantly reduced in endothelium-denuded strips from GTN-treated rabbits. In beta-escin-skinned smooth muscle, the ability of 8-bromoguanosine 3',5' cyclic monophosphate (8-Br-cGMP, a phosphodiesterase-resistant cGMP analogue) to relax the contraction induced by 0.3 muM Ca2+ was significantly reduced in GTN-treated rabbits.
3 In beta-escin-skinned smooth muscle, an inhibitor of conventional and/or novel PKCs, GF109203X (0.6 muM), inhibited the Ca2+-induced contraction and enhanced the 8-Br-cGMP-induced relaxation. However, since the relaxing ability of 8-Br-cGMP was found to be unchanged by GF109203X when contractions were amplitude-matched (0.2 muM Ca2+ alone vs 0.3 muM Ca2+ + GF109203X), the increase in the 8-Br-cGMP-response seen with GF109203X was probably due to its inhibitory action on the Ca2+-induced contraction. Furthermore, although the PKC activator phorbol 12,13-dibutyrate (PDBu, 0.1 muM) decreased the 8-Br-cGMP-induced relaxation of the Ca2+ (0.3 muM) contraction, this was probably due to its enhancement of the Ca2+-induced contraction since no such effect of PDBu was seen when the Ca2+-induced contractions were amplitude-matched (0.2 muM Ca2+ + PDBu vs 0.3 muM Ca2+ alone).
4 These results suggest that the relaxing response to cGMP is reduced in the smooth muscle of mesenteric resistance arteries in GTN-treated rabbits but that conventional and/or novel PKCs do not play a major role in maintaining this downregulation.
2 The relaxation responses to GTN and the nitric oxide donor NOC-7 were significantly reduced in endothelium-denuded strips from GTN-treated rabbits. In beta-escin-skinned smooth muscle, the ability of 8-bromoguanosine 3',5' cyclic monophosphate (8-Br-cGMP, a phosphodiesterase-resistant cGMP analogue) to relax the contraction induced by 0.3 muM Ca2+ was significantly reduced in GTN-treated rabbits.
3 In beta-escin-skinned smooth muscle, an inhibitor of conventional and/or novel PKCs, GF109203X (0.6 muM), inhibited the Ca2+-induced contraction and enhanced the 8-Br-cGMP-induced relaxation. However, since the relaxing ability of 8-Br-cGMP was found to be unchanged by GF109203X when contractions were amplitude-matched (0.2 muM Ca2+ alone vs 0.3 muM Ca2+ + GF109203X), the increase in the 8-Br-cGMP-response seen with GF109203X was probably due to its inhibitory action on the Ca2+-induced contraction. Furthermore, although the PKC activator phorbol 12,13-dibutyrate (PDBu, 0.1 muM) decreased the 8-Br-cGMP-induced relaxation of the Ca2+ (0.3 muM) contraction, this was probably due to its enhancement of the Ca2+-induced contraction since no such effect of PDBu was seen when the Ca2+-induced contractions were amplitude-matched (0.2 muM Ca2+ + PDBu vs 0.3 muM Ca2+ alone).
4 These results suggest that the relaxing response to cGMP is reduced in the smooth muscle of mesenteric resistance arteries in GTN-treated rabbits but that conventional and/or novel PKCs do not play a major role in maintaining this downregulation.
- リンク情報
- ID情報
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- DOI : 10.1038/sj.bjp.0705625
- ISSN : 0007-1188
- PubMed ID : 14718264
- Web of Science ID : WOS:000189177000002