We are comparing the blood pressure-lowering effects of two marketed medications, Coreg CR
and Toprol XL. Although both drugs reduce blood pressure by blocking the action of
noradrenaline on beta-receptors in the blood vessels, Coreg CR also blocks alpha-receptors,
which may provide added blood pressure-lowering. In addition, Coreg CR may have anti-oxidant
actions. Cells which line blood vessels (termed "endothelial cells") make nitric oxide (NO),
which relaxes the muscle cells encircling the blood vessels, causing a reduction in blood
pressure. When body cells use oxygen, they normally produce "free radicals", which can
destroy NO,leading to high blood pressure, heart damage and worsenimg of diabetes.
Antioxidants remove free radicals and prevent or repair this damage. In this study we will
measure endothelial cell function, blood vessel wall stiffness, NO in exhaled breath, and
blood levels of substances which reflect NO production and destruction to determine if a
pure beta-blocker (Toprol XL) differs from an alpha/beta blocker (Coreg CR) in these
effects. We will also examine the mechanism by which such differences might occur.
The following techniques will be used:
Endothelial function will be measured non-invasively by flow-mediated changes in pulsatile
blood volume in the finger-tips.
Vascular compliance (stiffness) will be assessed by tonometry of the radial pulse wave
("augmentation index") and diastolic puse wave analysis.
Plasma nitrate/nitrite levels mirror NO production and will be measured
spectrophotometrically by the Griess reaction.
Plasma nitrotyrosine, an in vivo marker of NO-dependent damage induced by reactive nitrogen
intermediates derived from NO, will be measured by ELISA.
Exhaled NO may provide an real-time measure of endothelial cell NO production and can be
measured by a hand-held device which contains an electrochemical detector sensitive to 5
1. Type 2 diabetes mellitus,
2. Stable antidiabetic regimen for 3 months
3. Hemoglobin A1c <8.6%
4. Stable antihypertensive medication regimen for 3 months or more, including either an
angiotensin-converting enzyme inhibitor or angiotensin receptor blocker
1. Any clinically significant abnormality on history, physical examination, or
laboratory testing which could preclude safe completion of the study
2. Significant cardiac conditions
3. Lung disease
4. Cigarette smoking
5. Chronic kidney disease (Stage 3 or greater)
6. Type 1 diabetes
7. Known contraindication to alpha- or beta-blocker therapy