Rapps J A, Myers P R, Zhong Q, Parker J L
Departments of Physiology and Medicine, Dalton Cardiovascular Research Center, University of Missouri, Columbia, USA.
Circulation. 1998 Oct 20;98(16):1675-83. doi: 10.1161/01.cir.98.16.1675.
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.
Collateral arteries isolated after 2 months exhibited markedly reduced endothelium-dependent relaxation in response to acetylcholine (ACh; 10(-10) to 10(-4) mol/L) and bradykinin (BK; 10(-11) to 10(-6) mol/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 with NT-nitro-L-arginine methyl ester (L-NAME; 100 micromol/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 micromol/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).
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.
关于冠状动脉侧支动脉成熟过程中血管舒缩控制机制的发育，目前所知甚少。因此，我们研究了在左冠状动脉回旋支近端放置阿梅氏环栓2、4和9个月后分离出的犬侧支动脉的内皮依赖性舒张功能。
与非侧支冠状动脉的舒张相比，2个月后分离出的侧支动脉对乙酰胆碱（ACh；10⁻¹⁰至10⁻⁴mol/L）和缓激肽（BK；10⁻¹¹至10⁻⁶mol/L）的内皮依赖性舒张明显降低（P<0.01）。相比之下，侧支动脉对硝普钠的非内皮依赖性舒张与非侧支动脉的舒张相比仅略有降低（P<0.05）。4个月和9个月后分离出的侧支动脉的内皮依赖性舒张显著增加，以至于在这些时期侧支动脉和非侧支动脉对ACh和BK的舒张没有显著差异。用Nω-硝基-L-精氨酸甲酯（L-NAME；100μmol/L）抑制一氧化氮合成显著抑制了所有非侧支动脉以及9个月后分离出的侧支动脉中ACh诱导的舒张。然而，单独使用L-NAME或吲哚美辛（5μmol/L）均未抑制4个月后分离出的侧支动脉中ACh介导的舒张。只有当动脉用30mmol/L K⁺预收缩并预先用L-NAME和吲哚美辛处理时（即一氧化氮、前列腺素和内皮衍生超极化因子的合成/作用被抑制时），ACh诱导的这些侧支动脉的舒张才被抑制。
犬冠状动脉侧支动脉的内皮依赖性舒张在2个月后尚未完全发育。4个月后，侧支动脉的内皮依赖性舒张与非侧支动脉的舒张相似，但这种舒张对一氧化氮合成的依赖性降低，对前列腺素和内皮衍生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舒张，与非侧支动脉相似。
