K+ channel blockers and cytochrome P450 inhibitors on acetylcholine-induced, endothelium-dependent relaxation in rabbit mesenteric artery

1999 ◽  
Vol 384 (1) ◽  
pp. 7-15 ◽  
Author(s):  
Seigo Fujimoto ◽  
Yosuke Ikegami ◽  
Mituharu Isaka ◽  
Tadahiro Kato ◽  
Kenji Nishimura ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Mesenteric Artery ◽  
K Channel ◽  
Channel Blockers ◽  
Rabbit Mesenteric Artery ◽  
P450 Inhibitors ◽  
Endothelium Dependent Relaxation

Pharmacology of ATP-sensitive K+ currents in smooth muscle cells from rabbit mesenteric artery

1995 ◽  
Vol 269 (5) ◽  
pp. C1112-C1118 ◽  
Author(s):  
J. M. Quayle ◽  
A. D. Bonev ◽  
J. E. Brayden ◽  
M. T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mesenteric Artery ◽  
Katp Channels ◽  
Muscle Cells ◽  
K Channel ◽  
Patch Clamp Technique ◽  
Functional Studies ◽  
Rabbit Mesenteric Artery ◽  
K Currents

The inference that ATP-sensitive K+ (KATP) channels are involved in arterial responses to the synthetic K+ channel openers, hypoxia, adenosine, and calcitonin gene-related peptide, has relied on the sensitivity of these responses to the sulfonylureas glibenclamide and tolbutamide and to tetraethylammonium (TEA+). The inhibition of KATP currents by glibenclamide, tolbutamide, and TEA+ was investigated in single smooth muscle cells from rabbit mesenteric artery by use of the whole cell patch-clamp technique. The synthetic K+ channel openers pinacidil (half-activation 0.6 microM), cromakalim (half-activation 1.9 microM), and diazoxide (half-activation 37.1 microM) activated K(+)-selective currents that were blocked by glibenclamide. Elevation of pipette (intracellular) ATP concentration decreased K+ currents induced by pinacidil. Half-inhibition of KATP currents by glibenclamide and tolbutamide occurred at 101 nM and 351 microM, respectively. KATP currents were also inhibited by external TEA+, with half-inhibition at 6.2 mM. The results indicate that glibenclamide is an effective inhibitor of KATP channels in arterial smooth muscle and that tolbutamide and TEA+ are much less effective. Furthermore, these results support numerous functional studies that have demonstrated that the vasorelaxations to K+ channel openers are inhibited by < 10 microM glibenclamide but not by < 1 mM TEA+.

scholarly journals Combination of Ca2+ -activated K+ channel blockers inhibits acetylcholine-evoked nitric oxide release in rat superior mesenteric artery

2006 ◽  
Vol 149 (5) ◽  
pp. 560-572 ◽  
Author(s):  
E Stankevičius ◽  
V Lopez-Valverde ◽  
L Rivera ◽  
A D Hughes ◽  
M J Mulvany ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Superior Mesenteric Artery ◽  
Mesenteric Artery ◽  
K Channel ◽  
Channel Blockers ◽  
Nitric Oxide Release

Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

1995 ◽  
Vol 269 (3) ◽  
pp. H805-H811 ◽  
Author(s):  
S. Najibi ◽  
R. A. Cohen
Keyword(s):  
Carotid Artery ◽  
Sodium Nitroprusside ◽  
Channel Blocker ◽  
Isometric Tension ◽  
K Channel ◽  
K Channels ◽  
Rabbit Carotid Artery ◽  
Cyclic Monophosphate ◽  
Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

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