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.
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