Faraci F M, Orgren K, Heistad D D
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Stroke. 1994 Jan;25(1):178-82. doi: 10.1161/01.str.25.1.178.
This study examined the hypotheses that (1) atherosclerosis impairs relaxation of the carotid artery in response to activation of adenosine triphosphate (ATP)-sensitive potassium channels and (2) regression of atherosclerosis restores the response toward normal.
Isometric tension was measured in rings of carotid artery taken from normal, atherosclerotic, and regression monkeys and precontracted submaximally with prostaglandin F2 alpha.
Relaxation in response to acetylcholine was less in atherosclerotic compared with normal arteries (5 +/- 6% versus 54 +/- 4% [mean +/- SE] in response to 3 x 10(-8) mol/L acetylcholine, P < .01). Relaxation in response to aprikalim, a direct activator of ATP-sensitive potassium channels, was also less in atherosclerotic than in normal arteries (32 +/- 7% versus 69 +/- 5% during 10(-6) mol/L aprikalim, P < .01). Relaxation in response to aprikalim but not to acetylcholine or nitroprusside was inhibited almost completely by glibenclamide (4 mumol/L), a selective inhibitor of ATP-sensitive potassium channels. Relaxation in response to low but not high (10(-6) to 10(-5) mol/L) concentrations of sodium nitroprusside was less in atherosclerotic than in normal arteries. Regression of atherosclerosis tended to restore responses to acetylcholine, but not responses to nitroprusside or aprikalim, toward normal.
These findings suggest that atherosclerosis impairs relaxation of the carotid artery in response to activation of ATP-sensitive channels. Impaired responses may be due, in part, to nonspecific impairment of relaxation. Regression of atherosclerosis did not restore responses of the carotid artery toward normal.
本研究检验了以下假设：（1）动脉粥样硬化会损害颈动脉对三磷酸腺苷（ATP）敏感性钾通道激活的舒张反应；（2）动脉粥样硬化的消退可使反应恢复正常。
测量取自正常、动脉粥样硬化及消退期猴的颈动脉环的等长张力，并用前列腺素F2α使其进行次最大预收缩。
与正常动脉相比，动脉粥样硬化动脉对乙酰胆碱的舒张反应较小（对3×10⁻⁸mol/L乙酰胆碱的反应分别为5±6%和54±4%[平均值±标准误]，P<0.01）。对ATP敏感性钾通道的直接激活剂阿普卡林的舒张反应，动脉粥样硬化动脉也低于正常动脉（在10⁻⁶mol/L阿普卡林作用期间分别为32±7%和69±5%，P<0.01）。ATP敏感性钾通道的选择性抑制剂格列本脲（4μmol/L）几乎完全抑制了对阿普卡林而非乙酰胆碱或硝普钠的舒张反应。与正常动脉相比，动脉粥样硬化动脉对低浓度（而非高浓度，10⁻⁶至10⁻⁵mol/L）硝普钠的舒张反应较小。动脉粥样硬化的消退倾向于使对乙酰胆碱的反应恢复正常，但对硝普钠或阿普卡林的反应未恢复正常。
这些发现提示动脉粥样硬化会损害颈动脉对ATP敏感性通道激活的舒张反应。反应受损可能部分归因于舒张的非特异性损害。动脉粥样硬化的消退并未使颈动脉反应恢复正常。
