Role of superoxide in impaired endothelium-dependent vasodilation of coronary arterioles from diabetic dogs

Diabetes mellitus (DM) has been shown to impair endothelial responses in several vascular beds. We examined vascular reactivity of isolated ventricular artenoles (diameter 94 ±10 urn) from control and alloxan (60 mg/kg) treated dogs (3-8 kg) after a 1 week duration of DM (serum glucose = 390 ±45 mg%). Epicardial coronary artenoles were mounted onto pipettes in Kreb's buffer (5.5 mM glucose for controls and 22 mM for DM, distending pressure 20 mmHg, 0 flow). After constriction with endothelin (30-50% of resting diameter) cumulative doses of endothelium-dependent vasodilators acetylcboline (ACh,10^-10-10^-4 M), bradykinin (10^-14 to 10^-7 M), and the calcium ionophorc A23187 (10^-1210^-7M) were added extraluminally and internal diameters measured by video microscopy. ACh curves were also performed in the presence of 250 units/ml Superoxide dismutase (SOD). Results: Responses to bradykinin and A23187 were not altered in vessels from diabetic dogs. Maximal relaxation to ACh was attenuated in artenoles from DM dogs. Complete relaxation was obtained in vessels from DM dogs in the presence of SOD. Mean ±SEM,p<0.05 vs. control. ED50 (μM) Max% Relaxation Max% Relaxation -Log M [ACh] to ACh to SNP Control (n=12) 7.51 ±0.32 100±3 107±2 DM (n=13) 7.13 ±0.19 81±499±3 DM + SOD (n=7) 6.91 ±0.30 95±4 95 ±5 We conclude that DM selectively impairs acetylcholine induced endothelium-dependent relaxation in coronary microcirculation due to excess availability of superoxide free radicals.