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 mumol/L vs 98 +/- 18 mumol/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.