Prevention of cerebral vasospasm in the rat by depletion or inhibition of substance P in conducting vessels.
Cisternal blood injection in the rat induces a biphasic angiographic vasospasm, with a maximal acute spasm at 10 minutes and a maximal late spasm at 2 days after the subarachnoid hemorrhage (SAH). Depletion of substance P-containing sensory nerves to the cerebral arteries with capsaicin prior to SAH prevents the development of both acute and late spasm. Intrathecal administration of the substance P antagonist spantide 2 hours prior to SAH also prevents the development of vasospasm, while spantide administration 1 hour before SAH only hinders the occurrence of late vasospasm. Intracisternal administration of spantide 2 hours post-SAH prevents the development of late vasospasm. This antagonist per se can induce a short-lasting dose-dependent angiographic vasoconstriction. Substance P-containing nerve fibers on the cerebral arteries could constitute the sensory link in a reflex arc system involved in the development of vasospasm in which the presence of blood in the subarachnoid space stimulates sensory substance P-containing nerve fibers on the cerebral arteries inducing a centripetal impulse to the A2-nucleus tractus solitarius setting into motion the events in the brain stem leading to acute and late vasospasm.
Neurosurgical Research Department, University Hospital, Lund, Sweden.
T J
TJ
Delgado-Zygmunt
M A
MA
Arbab
L
L
Edvinsson
I
I
Jansen
N A
NA
Svendgaard
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002533:Cerebral Angiography; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014661:Vasoconstriction
D013373:Substance P; C042867:spantide; D002211:Capsaicin