Taylor P D, Khan I Y, Hanson M A, Poston L
Maternal & Fetal Research Unit, Division of Reproductive Health, Endocrinology and Development, 10th Floor North Wing, St Thomas' Hospital, London SE1 7EH, UK.
J Physiol. 2004 Aug 1;558(Pt 3):943-51. doi: 10.1113/jphysiol.2002.018879. Epub 2004 Jun 11.
We recently reported vascular dysfunction in adult offspring of rats fed a fat-rich (animal lard) diet in pregnancy. This study reports further characterization of constrictor and dilator function in mesenteric and caudal femoral arteries from 180-day-old offspring of dams fed the high fat diet (OHF). Endothelium-dependent relaxation in response to acetylcholine (10(-9)-10(-5)m) was impaired in mesenteric small arteries from male and female OHF compared with offspring of dams fed normal chow (males (maximum percentage relaxation): OHF 67.92 +/- 2.89, n= 8 versus control 92.08 +/- 2.19, n= 8, P < 0.01). Substantial relaxation in response to acetycholine in control mesenteric arteries remained after inhibition of nitric oxide synthase, soluble guanylate cyclase and cyclo-oxygenase but was blocked by 25 mm potassium. This component of relaxation, attributed to EDHF, was significantly reduced in OHF mesenteric arteries compared with controls. However, EDHF played a minor role in acetylcholine-induced relaxation in both control and OHF femoral caudal arteries (male and female). In these arteries, in contrast to mesenteric vessels, acetylcholine-induced relaxation was significantly enhanced in OHF but only in males (ACh (maximum percentage relaxation): OHF 58.40 +/- 4.39, n= 8 versus male controls 32.18 +/- 6.36, P < 0.05). This was attributable to enhanced nitric oxide-mediated relaxation. In conclusion, reduced endothelium-dependent relaxation in OHF mesenteric arteries is due to impaired EDHF-mediated relaxation. This defect was not apparent in femoral arteries in which EDHF has a less prominent role.
我们最近报道了孕期喂食富含脂肪(动物猪油)饮食的大鼠成年后代存在血管功能障碍。本研究进一步报道了高脂饮食喂养母鼠180日龄后代肠系膜动脉和股尾动脉中收缩和舒张功能的特征。与喂食正常饲料母鼠的后代相比,高脂饮食喂养母鼠后代(OHF)的雄性和雌性肠系膜小动脉对乙酰胆碱(10⁻⁹ - 10⁻⁵m)的内皮依赖性舒张受损(雄性(最大舒张百分比):OHF 67.92 ± 2.89,n = 8,对照组92.08 ± 2.19,n = 8,P < 0.01)。在抑制一氧化氮合酶、可溶性鸟苷酸环化酶和环氧化酶后,对照肠系膜动脉对乙酰胆碱仍有显著舒张,但被25 mM钾阻断。这种归因于内皮依赖性超极化因子(EDHF)的舒张成分,与对照组相比,在OHF肠系膜动脉中显著降低。然而,EDHF在对照和OHF股尾动脉(雄性和雌性)的乙酰胆碱诱导舒张中起次要作用。与肠系膜血管相反,在这些动脉中,乙酰胆碱诱导的舒张在OHF中显著增强,但仅在雄性中如此(乙酰胆碱(最大舒张百分比):OHF 58.40 ± 4.39,n = 8,雄性对照组32.18 ± 6.36,P < 0.05)。这归因于一氧化氮介导的舒张增强。总之,OHF肠系膜动脉中内皮依赖性舒张降低是由于EDHF介导的舒张受损。这种缺陷在EDHF作用不突出的股动脉中不明显。