Abstract

This is a proposal to study the constrictor and dilator neuroeffector control mechanisms of the cerebral and extracerebral cranial circulation.
The specific aims i nclude: (1) characterization of the """"""""unusual"""""""" alpha-adrenoceptor found in the rabbit basilar artery, (2) testing the hypothesis that the dilator innervation to some cranial blood vessels involves two transmitters - acetylcholine and possibly vasoactive intestinal polypeptide and that this dilator effect is mediated by the tunica intima, (3) comparing the control of large pial arteries and their tributaries as small as 70 u OD, (4) elucidating the efferent vasodilator neural pathways to cerebral and extracerebral blood vessels, (5) determining the distribution of the dilator innervation within the head, (6) characterizing the significance of the increased level of the choline acetyl-transferase found in anterior facial veins, (7) determining whether the sites of transition of alpha-adrenoceptor characteristics, similar to those that occur along the vertebral and internal carotid artery are found at other embryological significant sites and whether they relate to other receptor types. These studies will be pursued in the cat and rabbit utilizing a variety of techniques (1) catecholamine histofluorescence, immunohistochemistry of polypeptides and transmission electron microscopy (2) drug induced neurogenic constriction and dilation elicited in vitro by electrical field stimulation and their pharmacological analysis using conventional as well as resistance vessel myographs (3) measurements of acetylcholine, norepinephrine, choline acetyltransferase activity, high affinity choline and specific neuronal norepinephrine uptake and (4) surgical denervation procedures. These studies should further our knowledge of the unique neural control systems of cerebral and other cranial vascular beds and provide knowledge that might lead to a better understanding of their role and the possibilities for pharmacological manipulation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032383-03
Application #
3343757
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1983-12-01
Project End
1988-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405

  Publications

Henrion, D; Bevan, J A (1995) Magnitude of flow-induced contraction and associated calcium influx in the rabbit facial vein is dependent upon the level of extracellular sodium. J Vasc Res 32:41-8
Henrion, D; Bevan, J A (1995) Intraluminal flow preferentially increases net sodium uptake in the rabbit facial vein. J Vasc Res 32:413-22
Wellman, G C; Bevan, J A (1995) Barium inhibits the endothelium-dependent component of flow but not acetylcholine-induced relaxation in isolated rabbit cerebral arteries. J Pharmacol Exp Ther 274:47-53
Dunn, W R; Wellman, G C; Bevan, J A (1994) Enhanced resistance artery sensitivity to agonists under isobaric compared with isometric conditions. Am J Physiol 266:H147-55
Germann, P; Laher, I; Poseno, T et al. (1994) Barbiturate attenuation of agonist affinity in cerebral arteries correlates with anesthetic potency and lipid solubility. Can J Physiol Pharmacol 72:963-9
Dodge, J T; Bevan, R D; Bevan, J A (1994) Comparison of density of sympathetic varicosities and their closeness to smooth muscle cells in rabbit middle cerebral and ear arteries and their branches. Circ Res 75:916-25
Laher, I; Germann, P; Bevan, J A (1994) Neurogenically evoked cerebral artery constriction is mediated by neuropeptide Y. Can J Physiol Pharmacol 72:1086-8
Henrion, D; Laher, I; Klaasen, A et al. (1994) Myogenic tone of rabbit facial vein and posterior cerebral artery is influenced by changes in extracellular sodium. Am J Physiol 266:H377-83
Gaw, A J; Bevan, J A (1993) Flow-induced relaxation of the rabbit middle cerebral artery is composed of both endothelium-dependent and -independent components. Stroke 24:105-9;discussion 109-10
Bevan, J A; Wellman, G C (1993) Intraluminal flow-initiated hyperpolarization and depolarization shift the membrane potential of arterial smooth muscle toward an intermediate level. Circ Res 73:1188-92

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