Restoration of the response of the middle cerebral artery of the rat to acidosis in hyposmotic hyponatremia by the opener of large-conductance calcium sensitive potassium channels (BK).

Hyposmotic hyponatremia (the decrease of extracellular concentration of sodium ions from 145 to 121 mM and the decrease of hyposmolality from 300 to 250 mOsm/kg HO) impairs response of the middle cerebral artery (MCA) to acetylcholine and NO donor (S-nitroso-N-acetyl-DL-penicillamine). Since acidosis activates a similar intracellular signaling pathway, the present study was designed to verify the hypothesis that the response of the MCA to acidosis is impaired during acute hyposmotic hyponatremia due to abnormal NO-related signal transduction in vascular smooth muscle cells. Studies performed on isolated, cannulated, and pressurized rat MCA revealed that hyposmotic hyponatremia impaired the response of the MCA to acidosis and this was associated with hyposmolality rather than with decreased sodium ion concentration. Response to acidosis was restored by the BK but not by the K channel activator. Patch-clamp electrophysiology performed on myocytes freshly isolated from MCAs, demonstrated that hyposmotic hyponatremia does not affect BK currents but decreases the voltage-dependency of the activation of the BK channels in the presence of a specific opener of these channels. Our study suggests that reduced sensitivity of BK channels in the MCA to agonists results in the lack of response of this artery to acidosis during acute hyposmotic hyponatremia.