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.