Role of gap junctions in endothelium-derived hyperpolarizing factor-mediated vasodilatation in rat renal artery
Abstract
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 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.
RESULTS:
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.
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.
Keywords:
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 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.
RESULTS:
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.
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.