The Contribution of BK Channels to Ischemic Reperfusion Changes in Cerebral Blood Flow

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Ischemic/reperfusion (I/R) damage of cerebral vessels is a complex dynamic process leading to hypoxic brain damage. To improve the outcome and treatment of the effects of I/R, an understanding of the molecular mechanisms of changes occurring in the cerebral vascular bed after recovery of blood flow is required in order to identify therapeutic intracellular targets. High-conductivity calcium-dependent potassium channels (BK) involved in the vasodilator reaction of cerebral vessels and highly sensitive to changes in oxygen levels can be considered as such targets. The work investigated the change in the contribution of BK channels to the rats pial arteries dilation after I/R. Using the method of in vivo vascular imaging in I/R and sham-operated rats, the number and degree of dilatation reactions in response to acetylcholine chloride (ACh, 10-7 M, 8 min) and exogenous hydrogen sulfide (H2S) donor sodium hydrosulfide (30 µM, 2 min) were compared before and after the use of the BK channel blocker tetraethylammonium chloride (2 mM, 5 min). It was found that I/R inhibit the dilatatory reaction. Changes in ACh-induced vasodilation persist for 21 days after I/R. Changes of H2S-mediated processes are noted only in the first 14 days and depend on the vessel size. These changes may be based on a gradually developing decrease in the contribution of BK channels to vasodilation, mainly expressed in large pial arteries. The decrease in the contribution of BK channels to dilation is most pronounced after 14 days and persists for 21 days after I/R.

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O. Gorshkova

Pavlov Institute of Physiology of the RAS

Autor responsável pela correspondência
Email: o_gorshkova@inbox.ru
Rússia, Saint Petersburg

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2. Fig. 1. Image of a section of the pial vascular network in the programme for measuring vessel diameter: (a) - original image; (b) - image after processing in the programme. Arrows indicate: 1 - pial artery; 2 - pial vein; 3 - mark for diameter measurement.

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3. Fig. 2. Number of arterial dilatations in ischaemic rats (I/R) at different intervals of the postischaemic period. Comparison with values in falsely operated rats (SO); *p < 0.05; **p < 0.01.

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4. Fig. 3. Change in the constrictor response to TEA exposure after I/R: (a) - number of constrictions (% of the total number of arteries studied); (b) - amplitude of constriction (% relative to the artery diameter before ACh or NaHS exposure). Differences are significant with respect to the corresponding values in falsely operated rats (SO); *p < 0.05; ***p < 0.0001.

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5. Fig. 4. Effect of VC channel blockade on the dilatatory response in response to ACh and NaHS in LO rats (SO) and ischaemic rats (I/R): (a, b) - number of dilatations (% of the total number of arteries studied); (c, d) - dilatation amplitude (% relative to the artery diameter before ACh or NaHS). Line - response to ACh or NaHS administration without TEA, taken as 100%. * - differences are statistically significant compared with falsely operated rats (SO); # - differences are significant with respect to values obtained without TEA application; #*p < 0.05, ## p < 0.01, ###p < 0.0001.

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