GANGLIONIC CONTROL OF MESENTERIC BLOOD VESSELS

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The abdominal prevertebral ganglia consist of the celiac, superior mesenteric and inferior mesenteric ganglia and these ganglia provide the sympathetic innervation of the abdominal and pelvic blood vessels. The activity in these neurons controls the physiological state of the splanchnic vascular bed. The level of activity in these neurons is integrated from neural and hormonal inputs; these inputs include efferent sympathetic outflow, primary sensory neurons and special enteric and vascular sensory neurons. It is the aim of this research to determine the mechanisms whereby each of the inputs to ganglia control and modulate the mesenteric circulation. The findings from these studies will have implications not only for the mesenteric vascular bed but also for all vascular beds where neural control is operative. Using electrophysiological, anatomical and pharmacological techniques these studies will determine the following: 1) the characteristics of the sensory inhibitory junction potential (IJP) and associated vasodilatation evoked in mesenteric artery by intestinal distension, including which nerves mediate the response and neurotransmitter(s) involved; 2) the comparative pharmacology of mesenteric arteries and veins to elucidate the mechanisms underlying the greater responsiveness of mesenteric veins to nerve activation; 3) the physiological and pharmacological properties of cholinergic muscarinic e.p.s.p.s. evoked physiologically with intestinal distension; 4) biophysical properties of prevertebral ganglionic neurons determined with patch-voltage clamp in dissociated neurons; 5) ionic mechanism(s) of muscarinic depolarizations in dissociated ganglionic neurons determined with patch-voltage clamp and single electrode voltage clamp; 6) mechanism(s) of depolarizations produced in ganglionic neurons by candidate peptide neurotransmitters substance P, vasoactive intestinal peptide and calcitonin gene-related peptide; 7) characterize sympathetic nerve vascular smooth muscle interactions by evaluating neuromuscular transmission in neuron-smooth muscle co-cultures. The results of these studies will provide a fundamental understanding of the ways in which the sympathetic nervous system controls blood vessels and will provide rationale for the treatment of vascular and gastrointestinal disorders that have a neurogenic component including hypertension, ischemia, and inflammatory bowel disorders.