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_Ca)

Abstract

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.

Cerebrovascular reactivity and cerebral perfusion of rats with acute liver failure: role of L‐glutamine and asymmetric dimethylarginine in L‐arginine‐induced response

“…Unless noted otherwise, reagents used to test the reactivity of isolated vessels were purchased from Sigma-Aldrich, RRID:SCR_008988. Middle cerebral arteries (MCAs) were isolated from the brain of control and TAA rats and located in an organ chamber filled with physiological saline solution buffered with MOPS (3-(N-morpholino) propanesulfonic acid), (MOPS-PSS) with 1% dialyzed bovine serum albumin (BSA, #A3912) addition (pH 7.4 adjusted by NaOH, POCH, Gliwice, Poland, #810925112), as it was described in detail previously (Aleksandrowicz et al 2017). The organ chamber was placed at the stage of inverted microscope (CKX41, Olympus, Hamburg, Germany) connected with a video camera and a monitor for analysis of inner diameters of the arteries.…”

Compromised regulation of the rat brain parenchymal arterioles in vasopressin‐associated acute hyponatremia

“…Differences between MCAs and PAs in our study are also noticeable in the reactivity of these vessels to an increase in extravascular K + concentration. Twenty mmol/L K + solution, used to verify the viability of isolated MCAs in our study, is a routine test used for this purpose 25‐28 . It occurred, however, that PAs are more responsive than MCAs to the increase in extravascular K + concentration which is demonstrated by the dilation of PAs to 10 mmol/L K + to a similar extent as the dilation of the MCAs to 20 mmol/L K + solution (88% vs. 85% of the basal diameter).…”

Effect of vasopressin-induced chronic hyponatremia on the regulation of the middle cerebral artery of the rat

“…Our previous studies indicate that acute hyponatremia, which was induced in vitro without the presence of vasopressin, did not affect autoregulation, but blunted the response of the MCA to ACh, NO donor, and acidosis [4, 5]. Acute hyponatremia also decreased the sensitivity of the BK Ca channels in vascular smooth muscle cells to agonists [4], which would explain the impaired response of the MCA to the abovementioned vasodilators.…”

“…Acute hyponatremia also decreased the sensitivity of the BK Ca channels in vascular smooth muscle cells to agonists [4], which would explain the impaired response of the MCA to the abovementioned vasodilators. The results of this study do not speak in favor of the impairment of the BK Ca channels in the MCA during vasopressin-induced chronic hyponatremia as the response of this vessel to ACh and NO donor is unchanged.…”