Selective Effects of Subarachnoid Hemorrhage on Cerebral Vascular Responses to 4-Aminopyridine in Rats

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Background and PurposeWe postulated that some abnormalities in cerebrovascular function after subarachnoid hemorrhage (SAH) may involve underlying alterations in K+ channel function. Thus, using pharmacological inhibitors, we assessed the influence of SAH on function of 2 types of K+ channel in regulation of basilar artery diameter in vivo and membrane potential (Em) in vitro.MethodsRats 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 responses to 4-aminopyridine (4-AP), 3-aminopyridine (3-AP), tetraethylammonium (TEA), serotonin, acetylcholine, and adenosine were compared in control and SAH rats. Additional studies using intracellular microelectrodes evaluated the effects of 4-AP and serotonin on Em of basilar arteries isolated from control and SAH rats.ResultsBaseline artery diameter was 236±5 μm in control rats and 220±7 μm 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. Constrictor 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 Em was −81±3 mV in control arteries 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 arteries.ConclusionsThese data suggest that 4-AP induces cerebral vasoconstriction in vivo through smooth muscle depolarization due to inhibition of voltage-dependent K+ channels. Furthermore, function of these K+ channels may be selectively reduced in the basilar artery after SAH and thus could contribute to cerebral vascular dysfunction.

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