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result sql = Upregulation of intermediate calcium-activated potassium channels counterbalance the impaired endothelium-dependent vasodilation in stroke-prone spontaneously hypertensive rats.
Upregulation of intermediate calcium-activated potassium channels counterbalance the impaired endothelium-dependent vasodilation in stroke-prone spontaneously hypertensive rats.
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char = Y;code = 89
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char = r;code = 114
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char = s;code = 115
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char = n;code = 110
char = c;code = 99
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char = a;code = 97
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char = t;code = 116
char = h;code = 104
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char = i;code = 105
char = t;code = 116
char = r;code = 114
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char = n;code = 110
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char = t;code = 116
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char = e;code = 101
char = r;code = 114
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char = -;code = 45
char = N;code = 78
char = A;code = 65
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char = E;code = 69
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char = 1;code = 49
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char = 0;code = 48
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char = u;code = 117
char = m;code = 109
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char = 0;code = 48
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char = m;code = 109
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char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = C;code = 67
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char = r;code = 114
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char = s;code = 115
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char = n;code = 110
char = s;code = 115
char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = n;code = 110
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char = v;code = 118
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char = s;code = 115
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = s;code = 115
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char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
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char = S;code = 83
char = H;code = 72
char = R;code = 82
char = S;code = 83
char = P;code = 80
char = .;code = 46
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char = I;code = 73
char = b;code = 98
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char = o;code = 111
char = x;code = 120
char = i;code = 105
char = n;code = 110
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char = 0;code = 48
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char = m;code = 109
char = u;code = 117
char = m;code = 109
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char = L;code = 76
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char = ,;code = 44
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char = w;code = 119
char = h;code = 104
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char = c;code = 99
char = h;code = 104
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char = ;code = 32
char = a;code = 97
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char = s;code = 115
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char = l;code = 108
char = e;code = 101
char = c;code = 99
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char = i;code = 105
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char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
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char = t;code = 116
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char = c;code = 99
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char = K;code = 75
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char = C;code = 67
char = a;code = 97
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char = ;code = 32
char = (;code = 40
char = B;code = 66
char = K;code = 75
char = (;code = 40
char = C;code = 67
char = a;code = 97
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char = );code = 41
char = ;code = 32
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char = h;code = 104
char = a;code = 97
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char = n;code = 110
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char = s;code = 115
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char = d;code = 100
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char = m;code = 109
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char = d;code = 100
char = i;code = 105
char = f;code = 102
char = y;code = 121
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char = E;code = 69
char = D;code = 68
char = H;code = 72
char = F;code = 70
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char = S;code = 83
char = H;code = 72
char = R;code = 82
char = S;code = 83
char = P;code = 80
char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = W;code = 87
char = K;code = 75
char = Y;code = 89
char = .;code = 46
char = ;code = 32
char = U;code = 85
char = C;code = 67
char = L;code = 76
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char = 1;code = 49
char = 6;code = 54
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char = 4;code = 52
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char = (;code = 40
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char = m;code = 109
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char = ,;code = 44
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char = S;code = 83
char = H;code = 72
char = R;code = 82
char = S;code = 83
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char = T;code = 84
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char = A;code = 65
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char = 3;code = 51
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char = 8;code = 56
char = 4;code = 52
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char = T;code = 84
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char = i;code = 105
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char = S;code = 83
char = K;code = 75
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char = T;code = 84
char = ;code = 32
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char = o;code = 111
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char = (;code = 40
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char = c;code = 99
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char = l;code = 108
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = r;code = 114
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char = n;code = 110
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char = v;code = 118
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
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result sql = Endothelial dysfunction has been linked to a decrease in nitric oxide (NO) bioavailability and attenuated endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation. The small (SK(Ca)) and intermediate (IK(Ca)) calcium-activated potassium channels play a key role in endothelium-dependent relaxation. Because the repressor element 1-silencing transcription factor (REST) negatively regulates IK(Ca) expression, we hypothesized that augmented REST and decreased IK(Ca) expression contributes to impaired endothelium-dependent vasodilation associated with hypertension. Acetylcholine (ACh) responses were slightly decreased in small mesenteric arteries from male stroke-prone spontaneously hypertensive rats (SHRSPs) versus arteries from Wistar Kyoto (WKY) rats. Incubation with N-nitro-L-arginine methyl ester (L-NAME; 100mumol/L) and indomethacin (100mumol/L) greatly impaired ACh responses in vessels from SHRSP. Iberiotoxin (0.1mumol/L), which is a selective inhibitor of large-conductance K(Ca) (BK(Ca)) channels, did not modify EDHF-mediated vasodilation in SHRSP or WKY. UCL-1684 (0.1mumol/L), which is a selective inhibitor of SKCa channels, almost abolished EDHF-mediated vasodilation in WKY and decreased relaxation in SHRSP. 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34; 10mumol/L) and charybdotoxin (0.1mumol/L), which are both IKCa inhibitors, produced a small decrease of EDHF relaxation in WKY but completely abrogated EDHF vasodilation in SHRSP. EDHF-mediated relaxant responses were completely abolished in both groups by simultaneous treatment with UCL-1684 and TRAM-34 or charybdotoxin. Relaxation to SK(Ca)/IK(Ca) channels agonist NS-309 was decreased in SHRSP arteries. The expression of SK(Ca) was decreased, whereas IK(Ca) was increased in SHRSP mesenteric arteries REST : expression was reduced in arteries from SHRSP. Vessels incubated with TRAM-34 (10mumol/L) for 24h displayed reduced REST expression and demonstrated no differences in IK(Ca). In conclusion, IK(Ca) channel upregulation, via decreased REST, seems to compensate deficient activity of SK(Ca) channels in the vasculature of spontaneously hypertensive rats.

Publication: Transl Res 2009 Oct ;154(4)::183-93. :doi: 10.1016/j.trsl.2009.07.003.
Publication Date: 2009 Oct
Study Author(s): Giachini, Fernanda R C;Carneiro, Fernando S;Lima, Victor V;Carneiro, Zidonia N;Dorrance, Anne;Webb, R Clinton;Tostes, Rita C;
Institution: Department of Physiology, Medical College of Georgia, Augusta, GA, USA; Department of Pharmacology, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA. [email protected]
Shortcut link to this study:
Endothelial dysfunction has been linked to a decrease in nitric oxide (NO) bioavailability and attenuated endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation. The small (SK(Ca)) and intermediate (IK(Ca)) calcium-activated potassium channels play a key role in endothelium-dependent relaxation. Because the repressor element 1-silencing transcription factor (REST) negatively regulates IK(Ca) expression, we hypothesized that augmented REST and decreased IK(Ca) expression contributes to impaired endothelium-dependent vasodilation associated with hypertension. Acetylcholine (ACh) responses were slightly decreased in small mesenteric arteries from male stroke-prone spontaneously hypertensive rats (SHRSPs) versus arteries from Wistar Kyoto (WKY) rats. Incubation with N-nitro-L-arginine methyl ester (L-NAME; 100mumol/L) and indomethacin (100mumol/L) greatly impaired ACh responses in vessels from SHRSP. Iberiotoxin (0.1mumol/L), which is a selective inhibitor of large-conductance K(Ca) (BK(Ca)) channels, did not modify EDHF-mediated vasodilation in SHRSP or WKY. UCL-1684 (0.1mumol/L), which is a selective inhibitor of SKCa channels, almost abolished EDHF-mediated vasodilation in WKY and decreased relaxation in SHRSP. 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34; 10mumol/L) and charybdotoxin (0.1mumol/L), which are both IKCa inhibitors, produced a small decrease of EDHF relaxation in WKY but completely abrogated EDHF vasodilation in SHRSP. EDHF-mediated relaxant responses were completely abolished in both groups by simultaneous treatment with UCL-1684 and TRAM-34 or charybdotoxin. Relaxation to SK(Ca)/IK(Ca) channels agonist NS-309 was decreased in SHRSP arteries. The expression of SK(Ca) was decreased, whereas IK(Ca) was increased in SHRSP mesenteric arteries REST : expression was reduced in arteries from SHRSP. Vessels incubated with TRAM-34 (10mumol/L) for 24h displayed reduced REST expression and demonstrated no differences in IK(Ca). In conclusion, IK(Ca) channel upregulation, via decreased REST, seems to compensate deficient activity of SK(Ca) channels in the vasculature of spontaneously hypertensive rats.
PMID: 19766962

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