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Uncontrolled Hypertension, Uncompensated Type II Diabetes, and Smoking Have Different Patterns of Vascular Dysfunction^*

^* From the Department of Pharmacology, Cardiovascular Pharmacology Laboratory, Faculty of Medical Sciences, State University of Campinas, Unicamp, Campinas, SP, Brazil.

Correspondence to: Heitor Moreno Jr, MD, PhD, Cardiovascular Pharmacology Division, Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), PO Box 6111, 13083-970 Campinas, São Paulo, Brazil; e-mail: hmoreno{at}uol.com.br

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)-B₂ 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-B₂ 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-B₂ were not significantly different in the four groups, but nitrite/nitrate concentrations were increased in diabetics compared to the control subjects (266 ± 47 µmol/L vs 98 ± 18 µmol/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.

Key Words: diabetes mellitus • endothelial function • nicotine • nitric oxide • thromboxane • vascular remodeling

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