The effects of hyperosmolar solutions on cerebral arterial smooth muscle.
The present study was conducted to clarify the effect of hyperosmolar solutions on the constrictor responses of cerebral arteries to vasoactive agents, in vitro. The canine basilar arteries under resting tension were slightly relaxed with both mannitol (0.5, 1 and 2%) and sucrose (1, 2, and 4%). Constrictor responses of canine basilar arteries to 40 mM K+, 10(-7) M serotonin or 10(-6) M prostaglandin F2 alpha (PGF2 alpha) were markedly suppressed by pretreatment with either mannitol or sucrose. The rate of suppression correlated well to osmolarity changes in the Kreb's solution. When the specimens were incubated in Ca++-free medium, 10(-6) M PGF2 alpha elicited small contractions. Addition of 1 mM Ca++ to the bath promptly elicited larger contractions. The large contractions in response to the influx of extracellular Ca++ were markedly suppressed by pretreatment with mannitol or sucrose, while the small contractions induced by intracellular Ca++ were not inhibited. In addition, the contractions induced by the addition of Ca++ to the specimens depolarized with 80 mM K+ in Ca++-free medium were dose-dependently inhibited with either mannitol or sucrose, while the caffeine-induced contractions in Ca++-free medium were not altered by mannitol. These results suggest that hyperosmolar solutions produce non-specific vasodilation of cerebral arteries by inhibiting the influx of external Ca++ rather than the release of intracellularly stored Ca++. This direct vasodilatory effect may account in part for the transient increase of cerebral blood flow following administration of hyperosmolar mannitol.
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D015237:Dinoprost; D004285:Dogs; D005260:Female; D006982:Hypertonic Solutions / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011460:Prostaglandins F / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D006982:Hypertonic Solutions; D007473:Ion Channels; D011460:Prostaglandins F; D012701:Serotonin; D008353:Mannitol; D013395:Sucrose; D015237:Dinoprost; D002118:Calcium