In diabetes, long term micro- and macro-vascular damage often underlies the functional decline in a number of organs. Using synchrotron imaging we are now able to detect small vessel calibres (∼40 μm vs. 200 μm using a conventional X-ray device) and quantify regional differences in resistance vessels of interest, even under conditions of high heart rate (>500 bpm).
Experiments were conducted at the Japanese Synchrotron, SPring-8, using anaesthetised Sprague–Dawley rats three weeks after treatment with vehicle (control) or streptozotocin (diabetic, 65 mg/kg i.p.). The right carotid artery was cannulated and angiograms of the coronary vasculature were recorded. Using cine-radiograms we investigated endothelium-dependent and -independent vasodilatory responses in individual coronary vessels, in vivo. Change is from baseline.
Diabetic animals had elevated blood glucose concentration (p < 0.001) and reduced final body weight (p < 0.001) and mean arterial pressure (p < 0.05). Vessel recruitment was lower in diabetics during acetylcholine (ACh, p < 0.05), while nitric oxide synthase (NOS) and cyclooxygenase (COX) blockade, resulted in a strong trend towards loss of visible microvessels (p = 0.059). Diabetic animals displayed numerous focal stenoses during NOS/COX blockade which persisted and increased after ACh infusion. Segmental constriction was also noted in diabetic rats during NOS/COX blockade which remained following ACh infusion. Diabetes was further associated with smaller vessel calibre in the 101–200 μm vessels during NOS/COX blockade (p < 0.05).
Synchrotron imaging provides a novel method to investigate coronary microvascular function in disease models, in vivo, and this study indicates that the early diabetic state is associated with localised and systemic impairment in coronary endothelial function in the diabetic microvasculature.
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© 2011 Published by Elsevier Inc.
