Sasaki T, Kassell N F, Fujiwara S, Torner J C, Spallone A
Stroke. 1986 Nov-Dec;17(6):1266-71. doi: 10.1161/01.str.17.6.1266.
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.
本研究旨在体外阐明高渗溶液对脑动脉对血管活性药物的收缩反应的影响。处于静息张力下的犬基底动脉，甘露醇（0.5%、1%和2%）和蔗糖（1%、2%和4%）均可使其轻度舒张。犬基底动脉对40 mM钾离子、10⁻⁷ M 5-羟色胺或10⁻⁶ M前列腺素F2α（PGF2α）的收缩反应，经甘露醇或蔗糖预处理后均显著受到抑制。抑制率与克雷布斯溶液中的渗透压变化密切相关。当标本在无钙离子培养基中孵育时，10⁻⁶ M PGF2α引起小幅度收缩。向浴槽中加入1 mM钙离子后，迅速引起大幅度收缩。甘露醇或蔗糖预处理可显著抑制细胞外钙离子内流引起的大幅度收缩，而细胞内钙离子诱导的小幅度收缩未受抑制。此外，在无钙离子培养基中用80 mM钾离子使标本去极化后，加入钙离子诱导的收缩，甘露醇或蔗糖均可使其呈剂量依赖性抑制，而在无钙离子培养基中咖啡因诱导的收缩不受甘露醇影响。这些结果表明，高渗溶液通过抑制细胞外钙离子内流而非细胞内储存钙离子的释放，对脑动脉产生非特异性血管舒张作用。这种直接的血管舒张作用可能部分解释了高渗甘露醇给药后脑血流量的短暂增加。
