This is a proposal to study (a) factors which regulate tone in pial arteries of animals and man and (b) the changes which occur in pial arteries following a permanent occlusion of the middle cerebral artery at its origin in animal models. The structural and functional changes in these arteries may limit the ability of anastomotic flow to adequately perfuse ischemic brain tissue. Conventional in vitro methods involving the use of the resistance artery myograph and a pressurized perfusion video imaging system will be used to study vascular segments. These will be obtained from arteries not smaller than those with unstretched lumen diameters of 50 m obtained from the rabbit and cat. These are vessels that contribute in a very significant way to cerebrovascular resistance. These techniques will be supplemented by studies involving other types of techniques - including light, fluorescence, scanning and transmission electron microscopy, biochemical estimations of norepinephrine and choline acetyltransferase and also vascular biochemical estimations of norepinephrine and choline acetyltransferase and also vascular smooth muscle electrophysiology and ion flux measurements. Specific objectives are to (1) analyze the basis of flow-induced increase and decrease in cerebrovascular tone, (2) characterize the neuroeffector features of some pial arteries that seem to have diverse properties by virtue of their size, location and function, (3) investigate low affinity sites for norepinephrine (extraceptors) found in cerebrovascular smooth muscle taking advantage of pial arteries that have such sites but lack alpha- adrenoceptors, (4) characterize the time-dependent, functional changes that occur in the perivascular nerves, vascular smooth muscle and endothelial cells of pial arteries distal to permanent occlusion of the middle cerebral artery and (5) characterize the neuroeffector mechanisms of human cerebral arteries, by examining segments taken during surgery and those obtained 2- 4 hours after death. The cerebral circulation is a complex vascular bed whose function reflects the interactions of many factors on blood vessels with a diversity of properties. Since vascular changes occur not only in stroke, migraine, transient ischemic attacks, subarachnoid hemorrhage, but also in the dementias, it is important to understand normal mechanisms of tone regulation and ways in which these mechanisms can change in disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032383-07
Application #
3343760
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1983-12-01
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
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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