Endothelial dysfunction in salt-sensitive essential hypertension.
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 micromol/d; P=0.033) compared with salt-resistant hypertensives (from 341+/-50 to 378+/-54 micromol/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.
Hypertension Unit, Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
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Bragulat
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de la Sierra
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Antonio
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D000109:Acetylcholine; D000328:Adult; D018660:Blood Pressure Monitoring, Ambulatory; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000097:blood / Q000652:urine; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood / Q000652:urine; D009599:Nitroprusside; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D016232:Endothelins; D009566:Nitrates; D012982:Sodium, Dietary; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D006152:Cyclic GMP; D000109:Acetylcholine