INHIBITION OF NITRIC OXIDE-INDUCED VASODILATION BY GAP JUNCTION INHIBITORS - A POTENTIAL ROLE FOR A CGMP-INDEPENDENT NITRIC-OXIDE PATHWAY

Studies have provided evidence for the role of gap junctional intercel lular communication in syncytial tissue function. This study tested th e hypothesis that the vasodilating effects of nitric oxide (NO) rely o n gap junctions. The effects of the gap junction inhibitors octanol (1 0(-4) mol/l) and heptanol (10(-3) mol/l) were examined on acetylcholin e-, the NO-donor S-nitroso-N-acetyl-penicillamine (SNAP)-, and guanosi ne-3',5'-cyclic monophosphate (cGMP)-induced relaxation. In addition, we tested varying concentrations of the gap junction inhibitor sucrose on SNAP-induced relaxation in the presence and absence of methylene b lue, an inhibitor of guanylate cyclase. Helical strips of rat thoracic aorta were placed in muscle baths for isometric force measurements. T issues treated with SNAP and cGMP were denuded of endothelium. Tissues incubated in octanol and heptanol exhibited 4- to 7-fold rightward sh ifts in acetylcholine-induced and 6- to 15-fold rightward shifts in SN AP-induced relaxation. Both octanol and heptanol produced 2-fold right ward shifts in cGMP-induced relaxation, comparably less in magnitude t han shifts produced in acetylcholine- and SNAP-induced relaxation. Suc rose (10(-2) to 10(-1) mol/l) produced a concentration-dependent right ward shift of up to 30-fold in relaxation to SNAP. Incubation with met hylene blue (10(-6) mol/l) altered this rightward shift only slightly, indicating a possible cGMP-independent mechanism for NO. These findin gs support the hypothesis that NO-induced vasodilation, through both c GMP-dependent and -independent pathways, relies on gap junctional comm unication.