Vitronectin receptor stimulation of remote vascular responses: role of connexin 43

We hypothesize that gap junctional communication along the vascular wall modulates remote responses. To test this, we employed both pharmacologic and genomic approaches to block connexin (C×)43 transcription, using the remote response to vitronectin receptor (VTR) stimulation as a model response. Arteriolar diameter and red blood cell velocity were determined in the cheek pouch preparation of anesthetized (pentobarbital, 70 mg/kg) hamsters (N=25). LM609 (VTR agonist) was micropipette applied to the termination of the arteriolar network; observations were made 1000 μm upstream at the entrance to the network. Control responses consist of an immediate increase in velocity (shear rate) followed by a dilation with a decrease in shear rate. Gap junctions were pharmacologically inhibited with 18-alpha-glycyrrhetinic acid micropipette application to the middle of the network; in a dose dependent fashion, remote dilation was attenuated, but shear rate did not change. Prevention of C×43 transcription (double strand RNA inhibition) likewise blocked only the dilation in a dose dependent fashion, and not shear. Together this suggests that gap junctions are involved in this response, and that C×43 is required for flow dependent dilation following stimulation of the vitronectin receptor.