Development of endothelium-dependent relaxation in canine coronary collateral arteries.

Development of endothelium-dependent relaxation in canine coronary collateral arteries.
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犬冠状侧支动脉内皮依赖性松弛的发展。

DOI:
10.1161/01.cir.98.16.1675
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发表时间:
1998
期刊:
影响因子:
37.8
通讯作者:
Parker,JL
Parker,JL
中科院分区:
医学1区
文献类型:
--
作者:
Rapps,JA;Myers,PR;Zhong,Q;Parker,JL

文献摘要

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背景:目前关于冠状动脉侧支成熟过程中血管舒缩控制机制的研究很少。因此,我们研究了在左旋冠状动脉近端周围放置ameroid闭塞器2、4和9个月后分离的犬侧支动脉内皮依赖性松弛。结果:与非侧支冠状动脉舒张相比,2个月后分离的侧支动脉在乙酰胆碱(ACh, 10−10 ~ 10−4mol/L)和缓激肽(BK, 10−11 ~ 10−6mol/L)作用下的内皮依赖性舒张明显降低(P<0.01)。与非侧支动脉舒张相比,硝普胺对侧支动脉内皮非依赖性舒张仅略有降低(P<0.05)。4个月和9个月后分离的侧枝动脉内皮依赖性舒张明显增加,在此期间侧枝动脉和非侧枝动脉对ACh和BK的舒张无显著差异。抑制一氧化氮合成withNΤ-nitro-l-arginine甲酯(L- name; 100 μmol/L)在9个月后显著抑制ach诱导的所有非侧支动脉和分离侧支动脉的舒张。然而,4个月后,L- name和吲哚美辛(5 μmol/L)均不能抑制乙酰胆碱介导的侧支动脉舒张。只有在用30mmol /L K+预缩动脉并用L- name和吲哚美辛预处理(即抑制一氧化氮、前列腺素和内皮源性超极化因子的合成/作用)时,乙酰胆碱诱导的侧支动脉舒张才会被抑制。结论:犬冠状动脉侧支血管内皮依赖性松弛在2个月后仍未完全发育。4个月后,内皮依赖性侧支动脉舒张与非侧支动脉舒张相似,但舒张表现出对一氧化氮合成的依赖性降低,前列腺素和内皮源性超极化因子的参与增加。发育9个月后,侧支动脉表现出正常的一氧化氮依赖性松弛,类似于非侧支动脉。
Background—Little information exists regarding development of vasomotor control mechanisms during coronary collateral artery maturation. Therefore, we studied endothelium-dependent relaxation of canine collateral arteries isolated 2, 4, and 9 months after placement of an ameroid occluder around the proximal left circumflex coronary artery.Results—Collateral arteries isolated after 2 months exhibited markedly reduced endothelium-dependent relaxation in response to acetylcholine (ACh; 10−10to 10−4mol/L) and bradykinin (BK; 10−11to 10−6mol/L) compared with relaxation of noncollateral coronary arteries (P<0.01). In contrast, endothelium-independent relaxation of collateral arteries to nitroprusside was only slightly reduced compared with relaxation of noncollateral arteries (P<0.05). Endothelium-dependent relaxation of collateral arteries isolated after 4 and 9 months was increased significantly, to the extent that relaxation to ACh and BK was not significantly different between collateral and noncollateral arteries at these periods. Inhibition of nitric oxide synthesis withNΤ-nitro-l-arginine methyl ester (L-NAME; 100 μmol/L) markedly inhibited ACh-induced relaxation in all noncollateral arteries and in collateral arteries isolated after 9 months. However, neither L-NAME nor indomethacin (5 μmol/L) alone inhibited ACh-mediated relaxation of collateral arteries isolated after 4 months. ACh-induced relaxation of these collateral arteries was only inhibited when arteries were preconstricted with 30 mmol/L K+and pretreated with L-NAME and indomethacin (ie, when synthesis/effects of nitric oxide, prostaglandins, and endothelium-derived hyperpolarizing factor were inhibited).Conclusions—Development of endothelium-dependent relaxation in canine coronary collateral arteries is not complete after 2 months. After 4 months, endothelium-dependent relaxation of collateral arteries is similar to relaxation of noncollateral arteries, but the relaxation exhibits decreased dependence on synthesis of nitric oxide and increased involvement of prostaglandins and endothelium-derived hyperpolarizing factor(s). After 9 months of development, collateral arteries exhibit normal nitric oxide–dependent relaxation, similar to noncollateral arteries.