The longterm goals are to determine what nerve fibers provide functional vasomotor innervation to small resistance vessels (arterioles and muscular venules) in the gastrointestinal (GI) and intracerebral microcirculation and to determine under what circumstances nonfunctional innervation can become functional. A new optical method for on-line tracking of outside diameter from in vitro preparations of microvessels whose outside diameters range from 10-100 (mu)m will be used in combination with pharmacological studies, immunohistochemistry, selective denervations and intracellular filling with dyes of identified vasomotor neurons in order to fulfil these goals. These techniques will be used to: (1) determine the immunohistochemical and functional innervation to submucosal arterioles and muscular venules in the normal guinea-pig ileum, colon and in the human colon; (2) identify individual vasomotor neurons and the course of their projections in the GI microcirculation of the guinea-pig; (3) determine changes in the immunohistochemical and functional innervation to GI submucosal microvessels in the guinea-pig after experimental disruptions to their sympathetic and/or sensory inputs and to their intrinsic (enteric) nerve supply; (4) provide quantitative pharmacological characterization of presynaptic and postsynaptic receptors mediating neurotransmitter release, vasoconstriction and vasodilation in arterioles and muscular venules of the GI microcirculation as well as in rat intracerebral arterioles. Results from these studies will provide hitherto unavailable pharmacological and physiological information about the microcirculation along the GI tract in the guinea-pig and human and the nerves that control contractility in this vascular network. Such information is essential in order to design drug, genetic or environmental manipulations that may lead to more precise control of blood pressure.
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