Received for publication April 15, 2008.
Revised July 6, 2008.
Accepted for publication July 16, 2008.

Gap junction inhibitors reduce endothelium-dependent contractions in the aorta of spontaneously hypertensive rats

Abstract

Experiments were designed to determine the effect of gap junction inhibitors on endothelium-dependent contractions. Isolated aortic rings of spontaneously hypertensive rats (SHR) were suspended in vitro for isometric force recording. The non-selective gap junction inhibitor, carbenoxolone reduced endothelium-dependent contractions to acetylcholine and the calcium ionophore A23187. There was no or modest effect of the gap peptides ⁴⁰Gap27, ^37,43Gap27 or ⁴³Gap26, when applied alone on endothelium-dependent contractions. However the combined treatment with the three gap peptides significantly decreased endothelium-dependent contractions. The combined inhibition of the three connexins was not as effective as carbenoxolone, suggesting the involvement of other connexins in the process of endothelium-dependent contraction. The present study shows the involvement of gap junctions in endothelium-dependent contractions of the SHR aorta, presumably that of the combination of connexins 37, 40, 43 rather than a single subtype of these proteins. Contractions of the vascular smooth muscle caused by U46619 and prostacyclin, but not to those of endoperoxides and phenylephrine were reduced only minimally by carbenoxolone. Thus, if gap junction signaling is involved in the contraction of the vascular smooth muscle to thromboxane-prostanoid (TP) receptor agonists, their contribution is small. This suggests that the reduction of endothelium-dependent contractions by carbenoxolone and the gap peptides cannot be attributed to the homocellular gap junctions between vascular smooth muscle, but more likely involves the homocellular gap junctions between endothelial cells and/or myoendothelial gap junctions.

Key words: EDCF, ROS, SHR, endothelium-derived contracting factor, gap junctions, reactive oxygen species