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

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.

Isolated renal arteries were mounted on a wire myograph apparatus were tissues treated with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester hydrochloride (NAME; 100 micromol/L) and indomethacin (10 micromol/L) and precontracted with phenylephrine (0.1 micromol/L). NAME and indomethacin treated carbachol (0.01-10 micromol/L)- or sodium nitroprusside (SNP; 1-300 nmol/L)-induced mediated relaxations were observed in the presence of gap junction inhibitors.

Carbachol produced a concentration-dependent relaxation in tissues treated with NAME (100 micromol/L) and indomethacin (10 micromol/L). This relaxation was not affected by hemoglobin (3 micromol/L), but was inhibited by charybdotoxin (200 nmol/L) and ouabain (30 micromol/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.

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.