Preik M, Kelm M, Feelisch M, Strauer B E
Department of Medicine, Heinrich Heine University Düsseldorf, Germany.
J Hypertens. 1996 Jul;14(7):903-8. doi: 10.1097/00004872-199607000-00014.
To assess the dilatory effectiveness of nitric oxide donors in resistance arteries of patients with arterial hypertension in comparison with that in those of normotensive controls.
Endothelium-dependent vasodilation has been demonstrated to be impaired in arterial hypertension. Besides disturbances in endothelial nitric oxide production a reduced vasodilatory effectiveness of nitric oxide might contribute to this phenomenon of endothelial dysfunction. We therefore investigated the dilatory responsiveness of resistance arteries to exogenous nitric oxide by means of administration of the nitric oxide donors glycerol trinitrate (GTN), isosorbide dinitrate (ISDN) and sodium nitroprusside (SNP) in hypertensive patients.
Forearm blood flow was measured by venous occlusion plethysmography at rest and during intra-arterial infusion of nitric oxide donors at increasing doses in 11 patients with arterial hypertension and in 10 age-matched normotensive controls.
Forearm blood flow at rest was comparable in the two groups and was dose-dependently increased by administration of either nitric oxide donor. In patients with arterial hypertension, blood flow responses to infusions of organic nitrates were significantly impaired over the entire dose-response curve compared with those of normotensive controls (220 nmol/min GTN 13.1 +/- 1.3 and 8.6 +/- 0.3 ml/min per 100 ml tissue; 212 nmol/min ISDN 9.9 +/- 0.7 and 5.8 +/- 1.0 ml/min per 100 ml tissue). Blood flow responses to infusion of the nitric oxide donor SNP were also profoundly impaired in the hypertensive patients, the extent of which impairment equalled that found with the organic nitrates. Within the entire set of normotensive and hypertensive subjects, maximal flow responses to either nitric oxide donor were inversely correlated with mean arterial blood pressure.
Dilation of resistance arteries in response to infusion of nitric oxide donors is impaired in hypertensive patients and the degree of this impairment depends critically on the severity of arterial hypertension. The reduced effectiveness of nitric oxide appears to be independent of the class of nitric oxide donor and thus of the mode of intravascular nitric oxide generation. These findings are likely to have important implications not only for our understanding of the pathophysiological mechanisms of endothelial dysfunction but also for nitric oxide donor therapy in arterial hypertension.
评估一氧化氮供体对动脉高血压患者阻力动脉的舒张效果，并与血压正常的对照者进行比较。
内皮依赖性血管舒张在动脉高血压中已被证实受损。除了内皮一氧化氮生成紊乱外，一氧化氮舒张效果降低可能也导致了这种内皮功能障碍现象。因此，我们通过给高血压患者施用一氧化氮供体三硝酸甘油酯（GTN）、二硝酸异山梨酯（ISDN）和硝普钠（SNP），研究了阻力动脉对外源性一氧化氮的舒张反应性。
通过静脉阻塞体积描记法测量11例动脉高血压患者和10例年龄匹配的血压正常对照者静息时以及动脉内递增剂量输注一氧化氮供体期间的前臂血流量。
两组静息时的前臂血流量相当，且施用任何一种一氧化氮供体均可使其剂量依赖性增加。与血压正常的对照者相比，动脉高血压患者在整个剂量反应曲线上对有机硝酸盐输注的血流反应明显受损（220 nmol/min GTN时，每100 ml组织分别为13.1±1.3和8.6±0.3 ml/min；212 nmol/min ISDN时，每100 ml组织分别为9.9±0.7和5.8±1.0 ml/min）。高血压患者对一氧化氮供体SNP输注的血流反应也严重受损，其受损程度与有机硝酸盐相当。在所有血压正常和高血压受试者中，对任何一种一氧化氮供体的最大血流反应与平均动脉血压呈负相关。
高血压患者对一氧化氮供体输注的阻力动脉舒张受损，且这种受损程度主要取决于动脉高血压的严重程度。一氧化氮效果降低似乎与一氧化氮供体类别无关，因此与血管内一氧化氮生成方式无关。这些发现不仅可能对我们理解内皮功能障碍的病理生理机制具有重要意义，而且对动脉高血压的一氧化氮供体治疗也具有重要意义。
