Clustering of endothelial markers of vascular damage in human salt-sensitive hypertension: influence of dietary sodium load and depletion.
The contributing role of vascular endothelium in the development of hypertension-related vascular damage is well accepted. Salt-sensitive hypertension is characterized by a cluster of renal, hormonal, and metabolic derangements that might favor the development of cardiovascular and renal damage. To evaluate endothelial involvement in salt-sensitive essential hypertension, plasma levels of several markers of endothelial damage such as endothelin-1 (ET-1), von Willebrand factor (vWf), and soluble (S-) adhesion molecules E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and 24-hour urinary albumin excretion (UAE) were measured in 39 nondiabetic, nonobese, never-treated essential hypertensive patients after intermediate (120 mmol/d), high (220 mmol/d), and low (20 mmol/d) NaCl diets. Patients were classified as salt sensitive (n=18) or salt resistant (n=21) according to their blood pressure responses to changes in dietary NaCl intake. Salt-sensitive hypertensives showed higher plasma ET-1 (P<0.05), vWf (P<0.005), and S-E-selectin levels (P<0.04) and increased UAE (P<0.05) than salt-resistant hypertensives. By contrast, circulating S-ICAM-1 and S-VCAM-1 concentrations were not significantly higher in salt-sensitive (596. 56+/-177.05 ng/mL and 541.06+/-157.84 ng/mL, respectively) than salt-resistant patients (516.86+/-147.99 ng/mL and 449.48+/-158.91 ng/mL, respectively). During the intermediate NaCl diet, plasma ET-1 responses to oral glucose load were greater in salt-sensitive (P<0. 05) than in salt-resistant patients. A marked (P<0.05) hyperinsulinemic response to oral glucose load was evident in salt-sensitive but not salt-resistant patients after each diet. This study shows increased plasma levels of the endothelium-derived substances E-selectin, vWf, and ET-1 in salt-sensitive hypertensives. Our findings support the hypothesis that salt sensitivity is correlated with an increased risk for developing hypertension-related cardiovascular damage.
Ferri
C
C
University "La Sapienza," Chair of I Clinica Medica, Andrea Cesalpino Foundation, Departments of Experimental Medicine, A.S.), University of L'Aquila, L'Aquila, Italy. clferri@axrma.uniroma1.it
Bellini
C
C
Desideri
G
G
Giuliani
E
E
De Siati
L
L
Cicogna
S
S
Santucci
A
A
D000328:Adult; D017920:Antiporters / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000209:etiology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D019087:Selectins / Q000097:blood; D012982:Sodium, Dietary / Q000008:administration & dosage*; D028021:Sodium-Potassium-Chloride Symporters; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
D017920:Antiporters; D015415:Biomarkers; D002352:Carrier Proteins; D019332:Endothelin-1; D019087:Selectins; D012982:Sodium, Dietary; D028021:Sodium-Potassium-Chloride Symporters; D019010:Vascular Cell Adhesion Molecule-1; C045885:sodium-lithium countertransporter; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol