Bartlett I S, Marshall Janice M
Department of Physiology, Division of Medical Sciences, The Medical School, Birmingham B15 2TT, UK.
Exp Physiol. 2003 Jul;88(4):497-507. doi: 10.1113/eph8802564.
Comparisons were made between responses evoked by noradrenaline (NA) in iliac artery rings from normoxic (N) rats and chronically hypoxic (CH) rats kept in 12 % O(2) for 3-4 weeks. At P(O(2)) of 100 mmHg, cumulative concentration-response curves (CCRC) to NA were greatly depressed in endothelium-intact (E+) rings, but not endothelium-denuded (E-) rings, of CH rats relative to N rats. However, CCRCs evoked by NA in E+ and E- rings during nitric oxide (NO) synthase inhibition were similar in N and CH rats. Reducing P(O(2)) to 55 mmHg depressed CCRCs to NA in E+ and E- rings of CH and N rats in the absence and presence of NO synthase inhibition. At P(O(2)) of 100 mmHg, CCRCs evoked by phenylephrine were comparable in E+ and E- rings of N and CH rats as were CCRCs for the relaxation evoked by isoprenaline, which were similarly rightward shifted by NO synthase inhibition. However, CCRCs evoked by the NO donor sodium nitroprusside were leftward shifted in E- rings of CH rats relative to N rats. Further, in the presence of the alpha(2) adrenoceptor inhibitor rauwolscine, CCRCs to NA were comparable in E+ rings of CH and N rats. Thus, the depressive effects of chronic hypoxia on NA-evoked contractions of iliac artery are additional to those of acute hypoxia. We propose that they reflect a facilitation of the contribution of NO to alpha(2) adrenoceptor-evoked relaxation that includes an increased sensitivity of the vascular smooth muscle of arteries from CH rats to NO.
对常氧(N)大鼠和在12%氧气环境中饲养3 - 4周的慢性缺氧(CH)大鼠的髂动脉环中去甲肾上腺素(NA)诱发的反应进行了比较。在100 mmHg的氧分压(P(O₂))下,与N大鼠相比,CH大鼠的内皮完整(E +)环中对NA的累积浓度 - 反应曲线(CCRC)大幅降低,但内皮剥脱(E -)环中未出现这种情况。然而,在一氧化氮(NO)合酶抑制期间,NA在N大鼠和CH大鼠的E +和E -环中诱发的CCRC相似。在不存在和存在NO合酶抑制的情况下,将P(O₂)降至55 mmHg会降低CH大鼠和N大鼠的E +和E -环中对NA的CCRC。在100 mmHg的P(O₂)下,苯肾上腺素诱发的CCRC在N大鼠和CH大鼠的E +和E -环中相当,异丙肾上腺素诱发的舒张反应的CCRC也是如此,它们都因NO合酶抑制而类似地向右移位。然而,与N大鼠相比,NO供体硝普钠诱发的CCRC在CH大鼠的E -环中向左移位。此外,在α₂肾上腺素能受体抑制剂萝芙木碱存在的情况下,CH大鼠和N大鼠的E +环中对NA的CCRC相当。因此,慢性缺氧对NA诱发的髂动脉收缩的抑制作用是急性缺氧之外的额外作用。我们认为,它们反映了NO对α₂肾上腺素能受体诱发的舒张作用的促进,这包括CH大鼠动脉血管平滑肌对NO的敏感性增加。