Role of gap junctions in endothelium-derived hyperpolarizing factor-mediated vasodilatation in rat renal artery

• 来源期刊: 中国药理学报（英文版）
• 关键词: carbachol endothelium-derived hyperpolarizing factor gap junction gap 27 peptide renal artery
• 年，卷（期）: 2004,（8）
• 页码范围: 1031-1037
• 页数: 7页
• 语种: 英文

摘要

AIM: To investigate the effects of gap junction inhibitors on endothelium-derived but nitric oxide (NO)- and prostacyclin (PGI2)-independent vasodilatations induced by carbachol in the rat isolated renal artery. METHODS:Isolated renal arteries were mounted on a wire myograph apparatus were tissues treated with the nitric oxide synthase inhibitor Nw-nitro-L-arginine methyl ester hydrochloride (NAME; 100 μmol/L) and indomethacin (10 μmol/L) and precontracted with phenylephrine (0.1 μmol/L). NAME and indomethacin treated Carbachol (0.01-10 μmol/L)- or sodium nitroprusside (SNP; 1-300 nmol/L)-induced mediated relaxations were observed in the presence of gap junction inhibitors. RESULTS: Carbachol produced a concentration-dependent relaxation in tissues treated with NAME (100 μmol/L) and indomethacin (10 μmol/L). This relaxation was not affected by hemoglobin (3 μmol/L), but was inhibited by charybdotoxin (200 nmol/L) and ouabain (30 μmol/L). The putative gap junction inhibitors, GAP 27 peptides with sequence homology to connexins 40 and 43 respectively reduced carbachol- but not SNP-induced relaxations mediated by endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations.The inhibition by the connexin 43 inhibitor was greater than that of the connexin 40 inhibitor. CONCLUSION: The results indicate the presence of gap junctions sensitive to 43GAP 27 and 40GAP 27 in the rat renal artery and each of these different types of gap junctions plays a role in the NO- and PGI2-independent relaxations induced by carbachol in this blood vessel. However, connexin 43 appears to play a more predominant role in mediating gap junction communications in the rat renal artery.