Uncontrolled hypertension, uncompensated type II diabetes, and smoking have different patterns of vascular dysfunction.

STUDY OBJECTIVES: We evaluated the vascular reactivity in healthy subjects, heavy smokers, uncompensated type II diabetics, and patients with uncontrolled essential hypertension. Plasma nitrite/nitrate, cyclic 3',5'-guanosine monophosphate (cGMP), and thromboxane (TX)-B(2) levels were measured. PARTICIPANTS: One hundred participants were classified into four groups: normal control subjects (n = 25), heavy smokers (n = 25), uncompensated type II diabetics (n = 25), and patients with uncontrolled essential hypertension (n = 25). INTERVENTIONS: The brachial artery diameter was measured by a high-resolution ultrasound technique before and after reactive hyperemia and glyceryl trinitrate (GTN), 0.4 mg, administration. Plasma nitrite/nitrate, cGMP, and TX-B(2) levels were also measured. RESULTS: Heavy smokers, uncompensated type II diabetics, and uncontrolled hypertensive patients showed impaired endothelium-dependent, nitric oxide (NO) flow-mediated vasodilatation (8.0 +/- 2.5%, 5.8 +/- 2.7%, and 7.2 +/- 3.3%, respectively [mean +/- SD]) when compared to the control subjects (12.6 +/- 3.6%; p < 0.01). Smokers had a normal endothelium-independent function induced by NO donor (GTN) [25.0 +/- 7.3% vs 25.3 +/- 8.5% for control subjects]. Uncompensated type II diabetics and patients with uncontrolled hypertension had impaired endothelium-independent responses (17.7 +/- 7.1% and 16.8 +/- 6.9%, respectively, vs 25.3 +/- 8.5 for normal control subjects; p < 0.05). Plasma levels of cGMP and TX-B(2) were not significantly different in the four groups, but nitrite/nitrate concentrations were increased in diabetics compared to the control subjects (266 +/- 47 micro mol/L vs 98 +/- 18 micro mol/L, p < 0.05). CONCLUSION: Both uncontrolled hypertension and type II diabetes mellitus, but not smoking, are associated with impaired vascular smooth-muscle reactivity induced by NO donors. However, only uncompensated type II diabetics showed an increase in plasma nitrite/nitrate levels, suggesting an association with excessive production and/or inactivation of NO.

Biochemical endothelial markers and cardiovascular remodeling in refractory arterial hypertension.

BACKGROUND: Hypertension is the most important and well established risk factor for atherosclerosis. The vascular and cardiac remodeling present in refractory hypertensive patients are related to endothelial dysfunction, a key factor in early atherogenesis and cardiovascular disease. However the mechanistic relationship among biochemical endothelial function markers, cardiovascular remodeling, and refractory hypertension is unknown. METHODS: We evaluated the left ventricular mass and function, carotid thickness, and plasma nitrate/nitrite (NO2/NO3), cyclic 3'-5'-guanosine monophosphate (cGMP), and thromboxane B2 (TXB2) levels in refractory hypertensive (RH; n = 20) and healthy (CONTROL; n = 20) subjects 22-65 years old. Carotid thickness, left ventricular mass index (LVMI), and left ventricular fraction ejection (LVFE) were estimated by duplex scan ultrasound. Nitrates/nitrites were assayed using the Griess reaction, and plasma cGMP and thromboxane B2 were determined by enzymatic immunoassay (EIA). RESULTS: Left ventricular mass index was higher in the RH group (138 +/- 20 vs. 108 +/-17 g/m2, p < 0.001) but there was no significant difference in the ejection fraction (67 +/- 5% vs. 69 +/- 4%). Pulse pressure (61 +/- 9 mmHg vs. 46 +/- 10 mmHg) and carotid thickness (1.59 +/- 0.22m vs. 1.04 +/- 0.14mm) were significantly higher (p < 0.001) in RH patients whereas NO2/NO3, cGMP, and thromboxane B2 plasma concentrations were similar in bot groups. CONCLUSION: There was no association between cardiovascular remodeling and the particular biochemical markers of endothelial function we assessed in refractory hypertensive patients.