Protective effect of beraprost sodium, a new chemically stable prostacyclin analogue, against the deterioration of baroreceptor reflex following transient global cerebral ischaemia in dogs

Abstract

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 (1ygkg-1min-1 i.v., infused for 15min just before ischaemia) completely prevented the decrease in BRS. Although the lower dose of beraprost (0.1pgkg-'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 highe ,e. 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 prostacyclinlike cytoprotective effect through membrane stabilization.

The effects of beraprost Na, a stable prostacyclin analog, on animal models of stroke

“…The effects of beraprost are similar to those of PGI, (Kovacs and O'Grady, 1984;Kainoh et al, 1990;Sakai et al, 1990). A cerebral cytoprotective effect of beraprost owing to the deterioration of the baroreceptor reflex following transient global cerebral ischemia in dogs was also reported (Kurihara et al, 1990). These data suggest that beraprost has protective effect on the cerebral ischemic damage.…”

Neuroprotective properties of prostaglandin I2 IP receptor in focal cerebral ischemia

“…It is used for treatment and prevention of global cerebral ischemia in dogs and for cardiovascular diseases in humans (Kurihara et al, 1990; Murakami et al, 2005). In our study, one group of WT mice was pretreated with a single dose of vehicle (saline) or 50 or 100 μ g/kg beraprost per os (p.o.)…”

Protection by nicorandil against the dysfunction of the central vagal baroreflex system following transient global cerebral ischaemia in dogs

“…However, at least in a canine model of myocardial ischaemia, it has been shown that nicorandil failed to increase PGI2 release into coronary venous blood and that indomethacin failed to affect the cardioprotective effect of nicorandil (Gross et al, 1989). Furthermore, the protective effect of beraprost in our previous study (Kurihara et al, 1990a) was observed only at a dose higher than that required to inhibit platelet aggregation. Therefore, it seems to be unlikely that the cerebroprotective effect of nicorandil is due to an increase in PGI2 formation.…”

“…However, such a cytoprotective effect of nicorandil has yet to be established in organs other than the heart. In this context, the present study was conducted to investigate a possible cerebroprotective effect of nicorandil in a canine model of transient global cerebral ischaemia in which we have already confirmed the cerebroprotective effects of some drugs including flunarizine (Kurihara et al, 1989b;1990b), ifenprodil (Kurihara et al, 1990b), beraprost (Kurihara et al, 1990a) and halothane (Kurihara et al, 1992). The results were compared with those obtained with nitroglycerin and nicardipine.…”