Postischemic cerebral blood flow and neuroeffector mechanisms.
The influence of neuroeffector mechanisms in the regulation of postischemic cerebral blood flow was investigated by microsphere determination in 8 cats after chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The animals were subjected to 90 min of reperfusion following 10 min of global ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical hyperemia 30 min after reperfusion was attenuated by up to 48% in cortical gray matter ipsilateral to the side of trigeminal ganglionectomy (p less than 0.01). Axon reflex mechanisms involving the release of neuropeptides from peripheral sensory nerve fibers, such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA), mediate this response. SP and NKA cause vasodilation by endothelium-dependent mechanisms (endothelium-dependent relaxing factor), whereas CGRP relaxes vascular smooth muscle by direct receptor interactions. Studies were therefore undertaken to determine the extent to which endothelium-dependent mechanisms mediate the hyperemia following global cerebral ischemia. In 7 intact cats, the postischemic response of pial arterioles to the topical application of acetylcholine (ACh; 10(-7) M), an endothelial-dependent vasodilator, was measured using a closed cranial window technique. Although ACh increased pial arteriolar caliber by 17% under resting conditions, the same dose elicited a vasoconstrictor response (87% of pre-ACh diameter 30 min after reperfusion) for the first 60 min of reperfusion after 10 min of ischemia. ACh-induced vasodilation was restored by 75 min (105%), but was less than control even at 120 min (109 vs. 117%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Macfarlane
R
R
Stroke Research Laboratory, Neurology and Neurosurgery Services, Massachusetts General Hospital, Harvard Medical School, Boston.
Moskowitz
M A
MA
Tasdemiroglu
E
E
Wei
E P
EP
Kontos
H A
HA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001783:Blood Flow Velocity; D002415:Cats; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D015171:Ganglionectomy; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D008863:Microspheres; D010841:Pia Mater / Q000098:blood supply; D012668:Trigeminal Ganglion / Q000601:surgery; D014664:Vasodilation / Q000187:drug effects
D000109:Acetylcholine