McIntyre M, Hamilton C A, Rees D D, Reid J L, Dominiczak A F
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.
Hypertension. 1997 Dec;30(6):1517-24. doi: 10.1161/01.hyp.30.6.1517.
A deficiency of nitric oxide may be responsible for the increased vascular resistance associated with human essential hypertension and that seen in animal models of hypertension. Premenopausal females are relatively protected from hypertension and cardiovascular complications. Levels of superoxide can influence the availability of nitric oxide. We hypothesize that there are differences in nitric oxide availability between stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) and that superoxide may be responsible for at least some of these differences. We studied vascular reactivity in endothelium-intact aortic rings from WKY and SHRSP. We measured nitric oxide synthase activity in endothelial cells removed from aortas and also measured circulating nitrite/nitrate levels. We found the response to N(G)-nitro-L-arginine methyl ester to be significantly greater in WKY compared with SHRSP (95% CI: 20 to 174; P=.015) and in females compared with males in WKY (95% CI: 143 to 333; P=.00004) and SHRSP (95% CI: 70 to 224; P=.0006). Endothelial nitric oxide synthase activity was significantly greater in SHRSP compared with WKY (95% CI: 2.3 to 17.6; P=.016). The EC50 for relaxation to carbachol was significantly greater in male rats compared with female rats (95% CI: -1.1 to -0.2; P=.003) within the SHRSP strain. The maximum relaxation to carbachol was significantly attenuated in stroke prone spontaneously hypertensive compared with Wistar-Kyoto rats (95% CI: 1.7 to 14.4; P=.015). Diethyldithiocarbamate had a significantly greater effect on the stroke prone spontaneously hypertensive rats' carbachol response than that of Wistar-Kyoto rats (95% CI: 14.3 to 47.0; P=.0008). We conclude that superoxide may be responsible for strain differences in vascular reactivity, whereas nitric oxide availability may be responsible for sex differences independently of endothelial nitric oxide synthase activity and superoxide.
一氧化氮缺乏可能是导致人类原发性高血压以及高血压动物模型中血管阻力增加的原因。绝经前女性相对不易患高血压和心血管并发症。超氧化物水平会影响一氧化氮的可利用性。我们推测，易患中风的自发性高血压大鼠（SHRSP）和Wistar-Kyoto大鼠（WKY）之间一氧化氮的可利用性存在差异，并且超氧化物可能至少是造成其中一些差异的原因。我们研究了WKY和SHRSP完整内皮主动脉环的血管反应性。我们测量了从主动脉分离出的内皮细胞中的一氧化氮合酶活性，还测量了循环中的亚硝酸盐/硝酸盐水平。我们发现，与SHRSP相比，WKY对N(G)-硝基-L-精氨酸甲酯的反应显著更大（95%置信区间：20至174；P = 0.015），并且在WKY中，雌性大鼠对其的反应比雄性大鼠更大（95%置信区间：143至333；P = 0.00004），在SHRSP中也是如此（95%置信区间：70至224；P = 0.0006）。与WKY相比，SHRSP中的内皮型一氧化氮合酶活性显著更高（95%置信区间：2.3至17.6；P = 0.016）。在SHRSP品系中，雄性大鼠对卡巴胆碱舒张反应的半数有效浓度（EC50）显著高于雌性大鼠（95%置信区间：-1.1至-0.2；P = 0.003）。与Wistar-Kyoto大鼠相比，易患中风的自发性高血压大鼠对卡巴胆碱的最大舒张反应显著减弱（95%置信区间：1.7至14.4；P = 0.015）。二乙基二硫代氨基甲酸盐对易患中风的自发性高血压大鼠卡巴胆碱反应的影响比对Wistar-Kyoto大鼠的影响显著更大（95%置信区间：14.3至47.0；P = 0.0008）。我们得出结论，超氧化物可能是血管反应性品系差异的原因，而一氧化氮的可利用性可能是性别差异的原因，且与内皮型一氧化氮合酶活性和超氧化物无关。
