Selective effects of subarachnoid hemorrhage on cerebral vascular responses to 4-aminopyridine in rats

Background and Purpose-We postulated that some abnormalities in cerebrovasc ular function after subarachnoid hemorrhage (SAH) may involve underlying al terations in K+ channel function. Thus, using pharmacological inhibitors, w e assessed the influence of SAH on function of 2 types of K+ channel in reg ulation of basilar artery diameter in vivo and membrane potential (E-m) in vitro. Methods-Rats were injected with saline (control) or autologous blood (SAH) into the cisterna magna. Two days later, effects of vasoactive drugs on the basilar artery were examined with a cranial window preparation. Vascular r esponses to 4-aminopyridine (4-AP), 3-aminopyridine (3-AP), tetraethylammon ium (TEA), serotonin, acetylcholine, and adenosine were compared in control and SAH rats. Additional studies using intracellular microelectrodes evalu ated the effects of 4-AP and serotonin on E-m of basilar arteries isolated from control and SAH rats. Results-Baseline artery diameter was 236+/-5 mu m in control rats and 220+/ -7 mu m in SAH rats (P < 0.05). 4-AP, but not 3-AP, constricted the basilar artery in control rats, and responses to 4-AP were reduced in SAH rats. Co nstrictor responses to TEA or serotonin were unaffected by SAH. Vasodilator responses to acetylcholine were impaired in SAH rats, whereas responses to adenosine were not different. Resting E-m was -81+/-3 mV in control arteri es and -79+/-3 mV in SAH arteries. Both 4-AP and serotonin depolarized the basilar artery, but only 4-AP-induced depolarization was impaired in SAH ar teries. Conclusions These data suggest that 4-AP induces cerebral vasoconstriction in vivo through smooth muscle depolarization due to inhibition of voltage-d ependent K+ channels. Furthermore, function of these K+ channels may be sel ectively reduced in the basilar artery after SAH and thus could contribute to cerebral vascular dysfunction.