The blood flow in the optic nerve head is normally autoregulated, little affected by the level of intraocular pressure (IOP). Such regulation may be achieved through response to tissue levels of oxygen and carbon dioxide, which reflect the balance between local tissue metabolism and the volume of local blood flow. Hypothetically in glaucoma this regulation is faulty in the optic nerve head, permitting ischemic damage when the circulation is challenged by elevation of IOP. Only a little is know of the local physiologic event by which autoregulations is achieved, but nothing about how it may become faulty, or how faulty autoregulation might be corrected. Vascular smooth muscle of arteries and arterioles and precapillary sphincters have considerable influence on distribution of blood flow to various tissue regions. We hypothesize that capillaries may provide local fine tuning of blood flow, at least in some tissues, and specially in the optic nerve and retina, and perhaps the rest of the central nervous system. If capillaries participate in local control of blood flow, it may be achieved through pericytes, contractile cells whose function is not known, found in the walls of capillaries, especially in the central nervous system, including retina and optic nerve. Pericyte contractile or relaxation response to changes in local oxygen tension, mediated through nitric oxide and other mediators, may permit local influence on blood flow in capillaries. Responses to carbon dioxide, pH, adenosine accumulation, and other local chemical changes may also participate in capillary autoregulation of blood flow. In this project we plan to study the relaxation responses of pericytes grown in cell culture to endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), and the modification of NO-induced relaxation by oxygen tension (pO2). Responses to be observed are cell contraction, changes in intracellular free calcium concentration, production of nitrite degradation products of NO, and changes in adenylate cyclase activity.
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