Ingram David G, Newcomer Sean C, Price Elmer M, Eklund Kevin E, McAllister Richard M, Laughlin M Harold
Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2798-808. doi: 10.1152/ajpheart.00899.2006. Epub 2007 Jan 26.
Current literature suggests that chronic nitric oxide synthase (NOS) inhibition has differential effects on endothelium-dependent dilation (EDD) of conduit arteries vs. arterioles. Therefore, we hypothesized that chronic inhibition of NOS would impair EDD of porcine left anterior descending (LAD) coronary arteries but not coronary arterioles. Thirty-nine female Yucatan miniature swine were included in the study. Animals drank either tap water or water with N(G)-nitro-L-arginine methyl ester (L-NAME; 100 mg/l), resulting in control and chronic NOS inhibition (CNI) groups, respectively. Treatment was continued for 1-3 mo (8.3 +/- 0.6 mg x kg(-1) x day(-1)). In vitro EDD of coronary LADs and arterioles was assessed via responses to ADP (LADs only) and bradykinin (BK), and endothelium-independent function was assessed via responses to sodium nitroprusside (SNP). Chronic NOS inhibition diminished coronary artery EDD to ADP and BK. Incubating LAD rings with L-NAME decreased relaxation responses of LADs from control pigs but not from CNI pigs such that between-group differences were abolished. Neither indomethacin (Indo) nor sulfaphenazole incubation significantly affected relaxation responses of LAD rings to ADP or BK. Coronary arteries from CNI pigs showed enhanced relaxation responses to SNP. In contrast to coronary arteries, coronary arterioles from CNI pigs demonstrated preserved EDD to BK and no increase in dilation responses to SNP. L-NAME, Indo, and L-NAME + Indo incubation did not result in significant between-group differences in arteriole dilation responses to BK. These results suggest that although chronic NOS inhibition diminishes EDD of LAD rings, most likely via a NOS-dependent mechanism, it does not affect EDD of coronary arterioles.
当前文献表明，慢性一氧化氮合酶（NOS）抑制对传导动脉与小动脉的内皮依赖性舒张（EDD）有不同影响。因此，我们推测慢性抑制NOS会损害猪左前降支（LAD）冠状动脉的EDD，但不会影响冠状小动脉的EDD。本研究纳入了39只雌性尤卡坦小型猪。动物分别饮用自来水或含N(G)-硝基-L-精氨酸甲酯（L-NAME；100 mg/l）的水，从而分别形成对照组和慢性NOS抑制（CNI）组。治疗持续1 - 3个月（8.3±0.6 mg·kg⁻¹·d⁻¹）。通过对ADP（仅LAD）和缓激肽（BK）的反应评估冠状动脉LAD和小动脉的体外EDD，并通过对硝普钠（SNP）的反应评估非内皮依赖性功能。慢性NOS抑制降低了冠状动脉对ADP和BK的EDD。用L-NAME孵育LAD环可降低对照组猪LAD的舒张反应，但对CNI组猪的LAD无此作用，从而消除了组间差异。吲哚美辛（Indo）或磺胺苯吡唑孵育均未显著影响LAD环对ADP或BK的舒张反应。CNI组猪的冠状动脉对SNP的舒张反应增强。与冠状动脉相反，CNI组猪的冠状小动脉对BK的EDD得以保留，对SNP的舒张反应未增加。L-NAME、Indo以及L-NAME + Indo孵育在小动脉对BK的舒张反应方面未导致显著的组间差异。这些结果表明，尽管慢性NOS抑制会降低LAD环的EDD，很可能是通过一种NOS依赖性机制，但它并不影响冠状小动脉的EDD。
