The overall objectives are to investigate: 1) the electrical and mechanical properties of isolated cerebral arterial smooth muscle; 2) the regional differences in these properties that may exist among the brain and peripheral vessels and; 3) the mechanisms underlying the selective acute and long-term effects of, and differential sensitivities to, calcium antagonists on cerebral and peripheral vasculature. Specific foci are: Comparative studies. Intracellular recordings of membrane potential and simultaneous tension measurements will be obtained from brain arterial (vertebral, basilar, middle cerebral, cerebellar) and pial arteriolar smooth muscle, in vitro. Changes in response to stimulation of the nerve supply, electrical stimulation of the smooth muscle directly, or application of vasoconstrictor drugs will be recorded.
The aims are to determine the relative vasoconstrictor contributions these three types of stimuli provide along the cerebrovascular tree and where the transition from peripheral (i.e. predominantly neurogenic) to cerebral (possibly mainly myogenic) type of electrical activity occurs. Acute versus long-term treatment with Ca antagonists. The effects of in vitro superfusion of calcium-antagonists on the above noted stimulus-evoked responses in these cerebral vessels will be examined. The electrical and mechanical activities of isolated cerebral vessels from animals chronically treated with calcium-antagonists will be compared with those from untreated animals. Fast resolution of ion movements across smooth muscle membrane and quantitative correlation of vessel constriction. Voltage-clamp studies of electrically-short, isolated segments of cerebral (pial) and peripheral (submucous plexus) arteriolar smooth muscle will be conducted. Membrane currents and constrictions underlying directly evoked action potentials and effects of calcium antagonists will be measured. These studies should help to predict which calcium antagonists may be most clinically beneficial in cerebrovascular dysfunctions such as migraine headache and brain ischemia in stroke; they may also help to explain why certain brain vessels are more susceptible to neurological disease states than are others.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL038940-01
Application #
3355435
Study Section
Physiology Study Section (PHY)
Project Start
1987-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Overall Medical
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Vanner, S; Jiang, M M; Surprenant, A (1993) Mucosal stimulation evokes vasodilation in submucosal arterioles by neuronal and nonneuronal mechanisms. Am J Physiol 264:G202-12
Vanner, S; Evans, R J; Matsumoto, S G et al. (1993) Potassium currents and their modulation by muscarine and substance P in neuronal cultures from adult guinea pig celiac ganglia. J Neurophysiol 69:1632-44
Jiang, M M; Surprenant, A (1992) Re-innervation of submucosal arterioles by myenteric neurones following extrinsic denervation. J Auton Nerv Syst 37:145-54
Andriantsitohaina, R; Surprenant, A (1992) Acetylcholine released from guinea-pig submucosal neurones dilates arterioles by releasing nitric oxide from endothelium. J Physiol 453:493-502
Bungardt, E; Vockert, E; Feifel, R et al. (1992) Characterization of muscarinic receptors mediating vasodilation in guinea-pig ileum submucosal arterioles by the use of computer-assisted videomicroscopy. Eur J Pharmacol 213:53-61
Evans, R J; Surprenant, A (1992) Vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation is mediated by the release of ATP. Br J Pharmacol 106:242-9
Vanner, S; Surprenant, A (1991) Cholinergic and noncholinergic submucosal neurons dilate arterioles in guinea pig colon. Am J Physiol 261:G136-44
Shen, K Z; Barajas-Lopez, C; Surprenant, A (1990) Functional characterization of neuronal pre and postsynaptic alpha 2-adrenoceptor subtypes in guinea-pig submucosal plexus. Br J Pharmacol 101:925-31
Vanner, S; Jiang, M M; Brooks, V L et al. (1990) Characterization of vasopressin actions in isolated submucosal arterioles of the intestinal microcirculation. Circ Res 67:1017-26
Galligan, J J; Jiang, M M; Shen, K Z et al. (1990) Substance P mediates neurogenic vasodilatation in extrinsically denervated guinea-pig submucosal arterioles. J Physiol 420:267-80

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