Endothelial Dysfunction in Salt-Sensitive Essential Hypertension

Abstract

The aim of this study was to evaluate endothelium-dependent and -independent vasodilation, as well as endothelium biochemical markers, in a group of essential hypertensive patients classified on the basis of salt sensitivity. Changes in forearm blood flow in response to acetylcholine, sodium nitroprusside, and N G -monomethyl- l -arginine (L-NMMA) infusion were determined by means of strain-gauge plethysmography. Moreover, plasma and urinary concentrations of nitrates, cGMP, and endothelin were measured during low (50 mmol/d) and high (250 mmol/d) salt intake. Salt-sensitive hypertension was diagnosed in 26 patients who exhibited a significant increase in 24-hour mean blood pressure assessed by ambulatory blood pressure monitoring after 1 week of high salt intake. Nineteen patients were considered salt resistant. Compared with salt-resistant hypertensives, salt-sensitive patients presented a significant lower ( P =0.005) maximal acetylcholine-induced vasodilation (21±6.3 versus 28±7.5 mL · 100 mL −1 · tissue · min −1 ). On the contrary, maximal sodium nitroprusside–induced vasodilation did not significantly differ between groups (22.4±4.5 versus 23.9±5.3 mL · 100 mL −1 · tissue · min −1 ). The decrease in maximal acetylcholine-induced vasodilation promoted by the coadministration of L-NMMA was significantly more pronounced in salt-resistant compared with salt-sensitive patients ( P =0.003). Finally, high salt intake promoted a significant decrease in 24-hour urinary nitrate excretion in salt-sensitive patients (from 443±54 to 312±54 μmol/d; P =0.033) compared with salt-resistant hypertensives (from 341±50 to 378±54 μmol/d). We conclude that salt-sensitive hypertension is associated with endothelial dysfunction characterized by a defective endothelium-dependent vasodilation. Impairment of the l -arginine–nitric oxide pathway may be responsible for this abnormal endothelial response.