Differential contractile responsiveness of femoral arteries from healthy and diabetic dogs: role of endothelium.

Phenylephrine-induced contraction and acetylcholine-induced relaxation of isolated femoral arterial strips (with and without endothelium) of diabetic (alloxan-treated) and metabolically healthy dogs were determined. Alloxan treatment did not change the contractile responsiveness to phenylephrine (PE) of the arteries with intact endothelium. After mechanical removal of the endothelial layer, however, the maximum force generated by the diabetic vessels (22.0 +/- 2.0 mN.m-2) significantly exceeded the maximum contraction produced by the nondiabetic arteries (14.6 +/- 1.8 mN.m-2). The dose-response curve of diabetic arteries to PE was steeper than it was in non-diabetic strips. The EC50 values for PE were similar in these two groups (0.45 +/- 0.12 and 0.58 +/- 0.20 mumol/l in diabetic and nondiabetic vessels, respectively). In the arteries with intact endothelium, acetylcholine produced concentration-related reduction of PE-induced tone. This endothelium-dependent relaxant activity of acetylcholine was similar in the healthy and diabetic arterial strips, IC50 for acetylcholine being 0.17 +/- 0.02 and 0.20 +/- 0.03 mumol/l, respectively. These results suggest that functional alteration of endothelium (probably an increased release of EDRF) prevails in diabetes. This may be important in reducing the hyper-responsiveness of diabetic arterial smooth muscle to PE.