Matrougui K, Maclouf J, Lévy B I, Henrion D
Institut National de la Santé et de la Recherche Médicale U141, IFR Circulation Lariboisière, Université Paris VII, France.
Hypertension. 1997 Oct;30(4):942-7. doi: 10.1161/01.hyp.30.4.942.
In human and experimental hypertension, flow (shear stress)-induced dilation in large arteries is attenuated and resistant to nitric oxide blockade. We tested the hypothesis that a defect in nitric oxide-and/or prostaglandin-dependent flow-induced dilation might occur in mesenteric resistance arteries from spontaneously hypertensive rats (SHR). We measured resistance mesenteric artery diameter in situ by intravital microscopy and simultaneously measured mesenteric arterial pressure in a collateral artery. The flow-diameter-pressure relationship was established in normotensive Wistar-Kyoto rats (WKY) and in SHR under control conditions and after endothelium removal, inhibition of nitric oxide synthesis with N omega-nitro-L-arginine methyl ester (10 micromol/L), or inhibition of prostaglandin synthesis with indomethacin (10 micromol/L). Production of prostaglandins was determined in the perfusate. Endothelium removal decreased artery diameter by 14 +/- 1.6% in WKY and 5 +/- 0.5% (P<.01 versus WKY) in SHR at a flow rate of 400 microL/min. In WKY, N omega-nitro-L-arginine methyl ester and indomethacin decreased resistance artery diameter by 12 +/- 3% (P<.001) and 5 +/- 2% (P<.01), respectively, at a flow rate of 400 microL/min; neither substance had any significant effect in SHR. In both strains, flow induced the production of 6-keto-prostaglandin F1alpha, the metabolite of prostacyclin; prostaglandin F2alpha; and thromboxane B2, the stable metabolite of thromboxane A2. Production of 6-keto-prostaglandin F1alpha and prostaglandin F2alpha was significantly lower in SHR than WKY, and TxB2 production was significantly higher in SHR than WKY. The present findings suggest that in SHR mesenteric resistance arteries, dilation in response to increases in flow was resistant to nitric oxide and prostaglandin synthesis blockade. A modification of the ratio of vasodilator to vasoconstrictor prostaglandins might be at least partly responsible for the decreased dilator response to flow in SHR.
在人类高血压和实验性高血压中，大动脉中血流（剪切应力）诱导的血管舒张减弱，且对一氧化氮阻断有抵抗作用。我们检验了这样一个假说：自发性高血压大鼠（SHR）肠系膜阻力动脉中可能存在一氧化氮和/或前列腺素依赖性血流诱导舒张功能缺陷。我们通过活体显微镜原位测量肠系膜阻力动脉直径，并同时测量侧支动脉中的肠系膜动脉血压。在正常血压的Wistar-Kyoto大鼠（WKY）以及SHR中，在对照条件下、去除内皮后、用Nω-硝基-L-精氨酸甲酯（10微摩尔/升）抑制一氧化氮合成或用吲哚美辛（10微摩尔/升）抑制前列腺素合成后，建立血流-直径-压力关系。在灌注液中测定前列腺素的生成。在流速为400微升/分钟时，去除内皮使WKY的动脉直径减小14±1.6%，使SHR的动脉直径减小5±0.5%（与WKY相比，P<0.01）。在流速为400微升/分钟时，Nω-硝基-L-精氨酸甲酯和吲哚美辛分别使WKY的阻力动脉直径减小12±3%（P<0.001）和5±2%（P<0.01）；这两种物质对SHR均无显著影响。在两种品系中，血流均诱导了前列环素的代谢产物6-酮-前列腺素F1α、前列腺素F2α以及血栓素A2的稳定代谢产物血栓素B2的生成。SHR中6-酮-前列腺素F1α和前列腺素F2α的生成显著低于WKY，而SHR中血栓素B2的生成显著高于WKY。目前的研究结果表明，在SHR肠系膜阻力动脉中，对血流增加的舒张反应对一氧化氮和前列腺素合成阻断有抵抗作用。血管舒张性前列腺素与血管收缩性前列腺素比例的改变可能至少部分导致了SHR中对血流的舒张反应降低。
