Abstract-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 (nϭ18) or salt resistant (nϭ21) according to their blood pressure responses to changes in dietary NaCl intake. Salt-sensitive hypertensives showed higher plasma ET-1 (PϽ0.05), vWf (PϽ0.005), and S-E-selectin levels (PϽ0.04) and increased UAE (PϽ0.05) than salt-resistant hypertensives. By contrast, circulating S-ICAM-1 and S-VCAM-1 concentrations were not significantly higher in salt-sensitive (596.56Ϯ177.05 ng/mL and 541.06Ϯ157.84 ng/mL, respectively) than salt-resistant patients (516.86Ϯ147.99 ng/mL and 449.48Ϯ158.91 ng/mL, respectively). During the intermediate NaCl diet, plasma ET-1 responses to oral glucose load were greater in salt-sensitive (PϽ0.05) than in salt-resistant patients. A marked (PϽ0.05) 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. (Hypertension. 1998;32:862-868.)Key Words: endothelium Ⅲ cell adhesion molecules Ⅲ vasorelaxation Ⅲ sodium Ⅲ blood pressure S alt-sensitive hypertension is characterized by a cluster of renal, hormonal, and metabolic derangements that might favor the development of cardiovascular and renal complications.1,2 In this regard, the vascular endothelium modulates platelet aggregation, adhesion molecule expression, and vascular smooth muscle cell replication, 3 all of which contribute to atherogenesis. Interestingly, salt-sensitive hypertension is characterized by impaired endothelium-dependent vasorelaxation. 4 Furthermore, circulating levels of the endotheliumderived peptide endothelin-1 (ET-1) are higher, 5 while urinary ET-1 excretion is lower 6 and more responsive to salt loading 7 in salt-sensitive than salt-resistant patients. Urinary albumin excretion (UAE), a well-known marker of vascular damage, 8 is associated with high plasma levels of von Willebrand factor (vWf,) 9 a glycoprotein released by damaged vascular endotheli...

A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 (mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002, r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.

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