CAPILLARIES DEMONSTRATE CHANGES IN MEMBRANE-POTENTIAL IN RESPONSE TO PHARMACOLOGICAL STIMULI

It has been proposed that capillaries can detect changes in tissue met abolites and generate signals that are communicated upstream to resist ance vessels. The mechanism for this communication may involve changes in capillary endothelial cell membrane potentials which are then cond ucted to upstream arterioles. We have tested the capacity of capillary endothelial cells in vivo to respond to pharmacological stimuli. In a hamster cheek pouch preparation, capillary endothelial cells were lab eled with the voltage-sensitive dye di-8-ANEPPS. Fluorescence from cap illary segments (75-150 mu m long) was excited at 475 nm and recorded at 560 and 620 nm with a dual-wavelength photomultiplier system. KCl w as applied using pressure injection, and acetylcholine (ACh) and pheny lephrine (PE) were applied iontophoretically to these capillaries. Cha nges in the ratio of the fluorescence emission at two emission wavelen gths were used to estimate changes in the capillary endothelial membra ne potential. Application of KCl resulted in depolarization, whereas a pplication of the vehicle did not. Application of ACh and PE resulted in hyperpolarization and depolarization, respectively. The capillary r esponses could be blocked by including a receptor antagonist (atropine or prazosin, respectively) in the superfusate. We conclude that the c apillary membrane potential is capable of responding to pharmacologica l stimuli. We hypothesize that capillaries can respond to changes in t he milieu of surrounding tissue via changes in endothelial membrane po tential.