The objective of the control of blood flow to the gut. Traditional theories hold that changes in tissue metabolism or intravascular pressures are the intrinsic regulators of intestinal blood flow. In 4 intestinal circulatory events an increase in blood flow is regulated locally, and the hyperemia is the common response to a fall in arterial pressure (""""""""pressure autoregulation""""""""), sympathetic nervous stimulation (""""""""escape""""""""), micellar lipid in the lumen of the gut (""""""""postprandial hyperemia""""""""), and release from arterial occlusion (""""""""reactive hyperemia""""""""). Intrinsic nerves, which regulate several intestinal functions, connect parenchymal cells to local blood vessels and utilize vasodilator peptides as neurotransmitters. We propose to test 2 hypotheses: 1) intrinsic, enteric, peptidergic nerves mediate the intestinal hyperemias observed during autoregulatory states; and 2) specificity exists among the peptide neurotransmitters in mediating individual autoregulatory states. Mucosal receptors stimulate afferent C fibers to direct impulses over 2 paths which influence vascular smooth muscle tone. The extrinsic pathway is via splanchnic afferent nerves to the CNS, which relays a signal over sympathetic postganglionic fibers, releasing norepinephrine, and constricting vascular smooth muscle. The intrinsic pathway involves an axonal reflex within the wall of the gut which releases vasodilator peptides, such as substance P(SP) and vasoactive intestinal peptide (VIP), thereby increasing intestinal blood flow. Hypotheses will be tested by determining hyperemic responses in the mesenteric circulation during pressure autoregulation, escape, postprandial hyperemia, and reactive hyperemia. These hyperemic responses to dissimilar stimuli will be measured with a pulsed-Doppler flowmeter in control rats and dogs, and in animals which have been pretreated with antagonists of the intrinsic, enteric, peptidergic nervous system, namely intraluminal lidocaine (to anesthetize mucosal sensory receptors), capsaicin (to deplete neuropeptides from primary sensory neurons), and specific an a against such dilator neurotransmitters as SP and VIP. Antagonists to extrinsic neural elements and paracrine vasodilator substances will also be studied. We expect to find that interventions which impede intrinsic neural functions in the gut will also inhibit its autoregulated hyperemias.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Surgery and Bioengineering Study Section (SB)
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University of Colorado Denver
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Jacobson, E D; Bunnett, N W (1997) G protein-coupled receptor signaling: implications for the digestive system. Dig Dis 15:207-42
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Berguer, R; Hottenstein, O D; Palen, T E et al. (1993) Bradykinin-induced mesenteric vasodilation is mediated by B2-subtype receptors and nitric oxide. Am J Physiol 264:G492-6

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