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 N-omega-nitro-L-arginine methyl ester hydrochloride (NAME; 100 mumol/L) and indomethacin (10 mumol/L) and precontracted with phenylephrine (0.1 mumol/L). NAME and indomethacin treated Carbachol (0.01-10 mumol/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 mumol/L) and indomethacin (10 mumol/L). This relaxation was not affected by hemoglobin (3 mumol/L), but was inhibited by charybdotoxin (200 mumol/L) and ouabain (30 mumol/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 - Tne results indicate the presence of gap junctions sensitive to (43)GAP 27 and (40)GAP 27 in the rat renal artery and each of these different types of gap junctions plays a role in the NO- and PGI(2)-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.