ARTERIOLAR REACTIVITY IN CONSCIOUS DIABETIC RATS - INFLUENCE OF AMINOGUANIDINE TREATMENT

The effect of 6 weeks' streptozotocin (STZ)-induced (70 mg/kg) diabete s and aminoguanidine (AG) treatment (50 mg/kg s.c. or 250-750 mg/l giv en in drinking water) on arteriolar reactivity to vasoactive substance s was investigated in conscious rats. Studies were performed in untrea ted control rats (n = 13), STZ-induced diabetic rats (n = 11), AG-trea ted control rats (n = 12), and AG-treated diabetic rats (n = 12). Rats were provided with a dorsal microcirculatory chamber that allowed int ravital microscopy of striated muscle arterioles of varying diameter ( A1, large; A2, intermediate; and A3, small arterioles) in conscious an imals. The mean arterial pressure (MAP) and arteriolar diameter respon ses to intravenous infusion of the following drugs were examined: the endothelium-dependent vasodilator acetylcholine (ACh; 3, 10, and 30 mu g . kg(-1) . min(-1)), the potassium-channel opener levcromakalim (LC ; 30 mu g/kg), and the vasoconstrictor agents ANG II (0.1 and 0.3 mu g . kg(-1) . min(-1)) and norepinephrine (NE; 0.2, 0.6, and 2.0 mu g . kg(-1) . min(-1)). Baseline MAP was lower in both diabetic groups vers us the nondiabetic groups (P < 0.05). AG treatment had no influence on baseline MAP. The absolute change in MAP after drug infusion tended t o be lower in the diabetic rats than in their nondiabetic Littermates. Arteriolar vasodilatory responses to ACh and LC were attenuated in th e diabetic animals (1 +/- 7 vs. 19 +/- 7% [P < 0.05] and 7 +/- 3 vs. 3 4 +/- 8% [P < 0.01] in A2, respectively). AG treatment of diabetic ani mals did not prevent the development of this disturbance. Vasoconstric tor responses were not influenced by the diabetic state. In the interm ediate arterioles of AG-treated control rats, a hyperresponse was obse rved after ANG II infusion (-10 +/- 2 vs. -2 +/- 2%; P < 0.05) and a h yporesponse was observed after ACh and LC infusion (2 +/- 3 and 15 +/- 6%, respectively; P < 0.05 vs. untreated control rats). These data in dicate that 6 weeks of experimental diabetes is associated with a decr eased endothelium-dependent and -independent vasodilatation. AG treatm ent had no beneficial effect on this disturbance.