VULNERABILITY OF CONDUCTED VASOMOTOR RESPONSE TO ISCHEMIA

Many vasoactive substances induce two responses, a direct effect at the site of application and a conducted response that spreads along the vessel length. In the microcirculation, we find that these two components of the vasomotor response display quite different sensitivities to occlusion and/or ischemia. Conducted vasomotor responses were induced in arterioles of the hamster cheek pouch by micropipette application of two test agents: phenylephrine (PE), which causes a receptor-mediated vasomotor response, and KCl, which causes an alteration in the membrane potential by a simple change in the K+ gradient. Ischemia was produced either by total occlusion of the vascular supply, which resulted in a complete cessation of flow in all vessels, or by venous occlusion, which was achieved by gradually inflating a pressurized cuff positioned across the pedicle of the pouch until venous return from the pouch was arrested while the feed arterioles remained patent. Both types of occlusion produced ischemia, the former with low intravascular pressure, the latter with high intravascular pressure. During both types of occlusion, arterioles were initially maximally dilated and unresponsive to both agonists, but over a subsequent 3- to 5-min period, resting arteriolar tone and local responses to both agonists returned. With total occlusion, the conducted response to KCl returned in parallel with the local response, whereas the conducted response to PE was diminished or absent. With venous occlusion, the local responses recovered as with total occlusion, but the conducted responses to both PE and KCI recovered as well. During total occlusion the conducted response to PE could be restored by increasing the vasomotor tone, either by elevation of superfusion solution Po, or by addition of prostaglandin F-2 alpha (10(-6) M) to the superfusate. Both total and venous occlusion reduced the mechanical length constant, indicating that some aspect of the conduction pathway per se may be vulnerable to ischemia. Furthermore, some portion of the intracellular signaling pathway associated with the generation of the conducted response to receptor-mediated events appears to require a significant level of vasomotor tone.