Pj. Javid et al., INHIBITION OF NITRIC OXIDE-INDUCED VASODILATION BY GAP JUNCTION INHIBITORS - A POTENTIAL ROLE FOR A CGMP-INDEPENDENT NITRIC-OXIDE PATHWAY, Journal of vascular research, 33(5), 1996, pp. 395-404
Citations number
45
Categorie Soggetti
Peripheal Vascular Diseas",Physiology,"Cardiac & Cardiovascular System
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.