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Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs
Author(s) -
Kurihara Junichi,
Sahara Tatsuhiro,
Kato Hitoshi
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14659.x
Subject(s) - prostacyclin , baroreceptor , ischemia , anesthesia , medicine , reflex , cerebral blood flow , medulla oblongata , vasodilation , blood pressure , heart rate , central nervous system
1 A possible cerebroprotective effect of a chemically stable prostacyclin analogue, beraprost sodium, was investigated in a canine model of cerebral ischaemia. Cerebral ischaemia was produced by the combined occlusions of the left subclavian and the brachiocephalic arteries with preceding ligations of the intercostal arteries. 2 The decrease in baroreceptor reflex sensitivity (BRS), measured by phenylephrine‐induced reflex bradycardia, following 5 min ischaemia was used to assess the cerebroprotective effect. 3 Beraprost (1 μg kg −1 min −1 i.v., infused for 15 min just before ischaemia) completely prevented the decrease in BRS. Although the lower dose of beraprost (0.1 μg kg −1 min −1 i.v.) failed to show such a protective effect, its inhibitory effect on ADP‐induced platelet aggregation was as potent as that of the higher dose. 4 The extent of decrease in BRS was inversely correlated with the extent of the residual blood flow in the medulla oblongata during ischaemia. Since beraprost did not affect the extent of the residual blood flow during ischaemia, its cerebroprotective effect could not be ascribed to the reduction of the degree of ischaemia by increasing collateral blood flow to the brain. 5 Post‐ischaemic reduction of the regional blood flow in the medulla and the cerebral cortex was completely prevented by the higher dose of beraprost. 6 The present study suggests that the cerebroprotective effect of beraprost may be independent of its anti‐aggregatory and vasodilator effects. It is possible that the protection may be due to a prostacyclin‐like cytoprotective effect through membrane stabilization.