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Uncontrolled hypertension, uncompensated type II diabetes, and smoking have different patterns of vascular
Juan Carlos Yugar-Toledo1, Jose Eduardo Tanus-Santos, Maricene Sabha
1Department of Pharmacology, Cardiovascular Pharmacology Laboratory, Faculty of Medical Sciences, State University of Campinas, Unicamp, Campinas, SP, Brazil.
Insights
Uncontrolled hypertension and type II diabetes mellitus impair vascular smooth muscle function, while smoking does not. Uncompensated diabetics show increased plasma nitrite/nitrate, indicating altered nitric oxide (NO) metabolism.
Area of Science:
- Cardiovascular Physiology
- Endothelial Function
- Vascular Reactivity
Background:
- Vascular reactivity is crucial for cardiovascular health.
- Endothelial dysfunction is implicated in various diseases.
- Nitric oxide (NO) plays a key role in vasodilation.
Purpose of the Study:
- To evaluate vascular reactivity in healthy individuals, heavy smokers, type II diabetics, and hypertensive patients.
- To assess plasma levels of nitrite/nitrate, cyclic guanosine monophosphate (cGMP), and thromboxane B2 (TX-B2).
Main Methods:
- Ultrasound measurement of brachial artery diameter before and after reactive hyperemia and glyceryl trinitrate (GTN) administration.
- Analysis of plasma biomarkers including nitrite/nitrate, cGMP, and TX-B2.
- Comparison of vascular responses across four participant groups: controls, smokers, diabetics, and hypertensives.
Main Results:
- Impaired endothelium-dependent vasodilation was observed in smokers, diabetics, and hypertensives compared to controls.
- Smokers exhibited normal endothelium-independent vasodilation, while diabetics and hypertensives showed impaired responses to GTN.
- Plasma nitrite/nitrate levels were elevated in diabetics, with no significant differences in cGMP or TX-B2 across groups.
Conclusions:
- Uncontrolled hypertension and type II diabetes mellitus are linked to impaired vascular smooth muscle reactivity to nitric oxide donors.
- Smoking did not demonstrate an association with impaired vascular reactivity in this study.
- Elevated plasma nitrite/nitrate in uncompensated diabetics suggests altered nitric oxide production or inactivation.
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.
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