Impaired effectiveness of nitric oxide-donors in resistance arteries of patients with arterial hypertension

OBJECTIVE: 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. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.