Background:

Studies using theoretical models have revealed the necessity of information transfer along blood vessels, most likely mediated via gap junctions, to achieve efficient blood flow distribution in microvascular networks. Its absence might lead to malperfusion. Here, we studied the effects of gap junction blockade on vessel diameter in chick chorioallantoic membrane (CAM) networks by intravital microscopy.

Methods:

We analysed the effects of the gap junction inhibitors carbenoxolone (175 µM, CBX), palmitoleic acid (100 µM, PA) and GAP27 (1000 µM) on vessel diameter. Maximal vasodilation (acetylcholine 10 µM, adenosine 100 µM, papaverine 200 µM, sodium nitroprusside 10 µM) allowed examining the relative contribution of changes in vessel structure and vascular tone.

Results:

All three gap junction inhibitors led to a decrease in both arterial and venous diameter. After 3h, diameters of arteries and veins decreased to 0.55 and 0.54 (relative to PBS control; CBX), 0.77 and 0.81 (PA) and 0.82 and 0.76 (GAP27). For CBX, about half (59%, 46%) of the diameter reduction was caused by structural adaptation, the rest by an increase in vascular tone. After 6h, diameter reduction was unchanged (0.55 and 0.45) but mainly caused by structural adaptation (96% and 88%).

Conclusion:

The present findings show the importance of gap junction based communication for developing microvascular networks. Gap junction blockade causes a substantial decrease in vessel diameter with an initial increase in vascular tone and a subsequent change of vessel structure.