ABSTRACT
The impact of diabetes on endothelium-dependent hyperpolarization and relaxation was compared in mesenteric and femoral arteries of rats in which the functional complement of endothelial vasodilators is different. Arteries, 200-300 um in diameter, obtained from rats following eight weeks of streptozotocin-induced diabetes and from their age-mat ched euglycaemic controls, were mounted on a Mulvany-style myograph. Using con ventional intracellular glass microelectrodes, the cell membrane potential was measured, simultaneously with isometric tension, in arteries depolarized and constricted with phenylephrine. Acetylcholine evoked relaxation in mesenteric and femoral arteries of control rats and the hyperpolarization was ten-fold larger in the mesenteric than in the femoral arteries. N^-nitro-L-arginine methylester ( L - N A M E ) abolished the responses in the femoral artery and shifted the concentration-response curves to the right in mesen teric artery, although maximal hyperpolarization and relaxation were still achieved. Indomethacin had no effect in either artery. Diabetes was without effect on the responses in the femoral artery. Although the maximal relaxation was unaltered in the mesenteric artery, the p D 2 for acetylcholine was shifted significantly to the right in the diabetics and the maximal hyperpolarization was reduced by half. The shift in the relaxation curve to the right by L - N A M E was the same as in the controls and the maximal amplitudes of the hyperpolarization and relaxation were reduced to 19 and 58%, respectively. Vitamin E for 8 weeks preserved the nitric oxide-dependent relaxations in both control and diabetic mesenteric arteries but impaired the EDHF-dependent responses, particularly in the arteries from euglycaemic animals.
