Role of calcium in the constriction of isolated cerebral arteries

Calcium entry blockers (CEB) have been used in the experimental treatment or prevention of many cerebrovascular disorders including stroke, post-ischemic hypoperfusion after cardiac arrest, cerebral vasospasm after subarachnoid hemorrhage, and migraine headache. However, the mechanism of action of these drugs on the cerebral circulation is poorly understood. This study examined the effects of calcium antagonists, Ca2+-deficient solutions, and vasocostrictors on cerebrovascular tone and 45Ca fluxes, to determine the role of calcium in cerebral arterial constriction. A Scatchard plot of 45Ca binding to BMCA showed that Ca2+ was bound at either low or high affinity binding sties. The four vasoconstrictors (potassium, serotonin, PGF/sub 2 α/, or SQ-26,655) each increased low affinity 45Ca uptake into BMCA. The results demonstrate that: (1) Potassium and serotonin constrict BMCA mainly by promoting Ca2+ influx through CEB-sensitive channels; (2) PGF/sub 2 α/ and SQ-26,655 constrict BMCA in part by promoting Ca2+ influx through CEB-sensitive channels, and in part by releasing Ca2+ from depletable internal stores; (3) The major action of CEB on BMCA is to block vasoconstrictor-induced Ca2+ uptake through both potential-operated (K+-stimulated) and receptor-operated channels