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

AIM: To investigate the effects of gap junction inhibitors on endothelium-derived but nitric oxide (NO)- and prostacyclin (PGI ₂)-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 Nω-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.