Woodman Christopher R, Ingram David, Bonagura John, Laughlin M Harold
Department of Biomedical Sciences, University of Missouri, Columbia, MO, USA.
Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2362-8. doi: 10.1152/ajpheart.01026.2005. Epub 2006 Jan 6.
We tested two hypotheses: 1) that the effects of hypercholesterolemia on endothelial function in femoral arteries exceed those reported in brachial arteries and 2) that exercise (Ex) training enhances endothelium-dependent dilation and improves femoral artery blood flow (FABF) in hypercholesterolemic pigs. Adult male pigs were fed a normal fat (NF) or high-fat/cholesterol (HF) diet for 20 wk. Four weeks after the diet was initiated, pigs were Ex trained or remained sedentary (Sed) for 16 wk, thus yielding four groups: NF-Sed, NF-Ex, HF-Sed, and HF-Ex. Endothelium-dependent vasodilator responses were assessed in vivo by measuring changes in FABF after intra-arterial injections of ADP and bradykinin (BK). Endothelium-dependent and -independent relaxation was assessed in vitro by measuring relaxation responses to BK and sodium nitroprusside (SNP). FABF increased in response to ADP and BK in all groups. FABF responses to ADP and BK were not impaired by HF but were improved by Ex in HF pigs. BK- and SNP-induced relaxation of femoral artery rings was not altered by HF or Ex. To determine whether the mechanism(s) for vasorelaxation of femoral arteries was altered by HF or Ex, BK-induced relaxation was assessed in vitro in the absence or presence of N(G)-nitro-l-arginine methyl ester [l-NAME; to inhibit nitric oxide synthase (NOS)], indomethacin (Indo; to inhibit cyclooxygenase), or l-NAME + Indo. BK-induced relaxation was inhibited by l-NAME and l-NAME + Indo in all groups of femoral arteries. Ex increased the NOS-dependent component of endothelium-dependent relaxation in NF (not HF) arteries. Indo did not inhibit BK-induced relaxation. Collectively, these results indicate that hypercholesterolemia does not alter endothelial function in femoral arteries and that Ex training improves FABF responses to ADP and BK; however, the improvement cannot be attributed to enhanced endothelial function in HF femoral arteries. These data suggest that Ex-induced improvements in FABF in HF arteries are mediated by vascular adaptations in arteries/arterioles downstream from the femoral artery.
1）高胆固醇血症对股动脉内皮功能的影响超过肱动脉所报道的影响；2）运动（Ex）训练可增强高胆固醇血症猪的内皮依赖性舒张并改善股动脉血流量（FABF）。成年雄性猪被喂食正常脂肪（NF）或高脂/高胆固醇（HF）饮食20周。在开始饮食四周后，猪进行Ex训练或保持久坐不动（Sed）16周，从而产生四组：NF-Sed、NF-Ex、HF-Sed和HF-Ex。通过测量动脉内注射ADP和缓激肽（BK）后FABF的变化，在体内评估内皮依赖性血管舒张反应。通过测量对BK和硝普钠（SNP）的舒张反应，在体外评估内皮依赖性和非依赖性舒张。所有组中，FABF均随ADP和BK增加。HF并未损害FABF对ADP和BK的反应，但Ex改善了HF猪的FABF反应。HF或Ex未改变BK和SNP诱导的股动脉环舒张。为确定HF或Ex是否改变了股动脉血管舒张的机制，在不存在或存在N（G）-硝基-L-精氨酸甲酯[l-NAME；抑制一氧化氮合酶（NOS）]、吲哚美辛（Indo；抑制环氧化酶）或l-NAME + Indo的情况下，在体外评估BK诱导的舒张。在所有股动脉组中，l-NAME和l-NAME + Indo均抑制BK诱导的舒张。Ex增加了NF（而非HF）动脉中内皮依赖性舒张的NOS依赖性成分。Indo未抑制BK诱导的舒张。总体而言，这些结果表明高胆固醇血症不会改变股动脉的内皮功能，且Ex训练可改善FABF对ADP和BK的反应；然而，这种改善不能归因于HF股动脉内皮功能的增强。这些数据表明，Ex诱导的HF动脉FABF改善是由股动脉下游动脉/小动脉的血管适应性介导的。
