EFFECT OF L-ARGININE ON REACTIVITY OF HAMSTER-CHEEK POUCH ARTERIOLES DURING DIABETES-MELLITUS

The goal of this study was to determine whether exogenous application of L-arginine could restore impaired agonist-induced increases in arte riolar diameter during diabetes mellitus. We used intravital microscop y to examine reactivity of cheek pouch arterioles (50 mu m in diameter ) in nondiabetic and diabetic (2 weeks after injection of streptozotoc in) hamsters in response to histamine and substance P. In nondiabetic hamsters histamine (1.0 and 5.0 mu M) dilated cheek pouch arterioles b y 15 +/- 1 and 22 +/- 1%, respectively, and substance P (50 and 100 nM ) dilated arterioles by 14 +/- 3 and 21 +/- 4%, respectively. In addit ion, dilatation of arterioles in response to histamine and substance P in nondiabetic hamsters was abolished by application of an enzymatic inhibitor of nitric oxide synthase (L-NMMA). In contrast, histamine- a nd substance P-induced increases in arteriolar diameter were markedly reduced in diabetic hamsters. Histamine (1.0 and 5.0 mu M) dilated art erioles by only 5 +/- 1 and 4 +/- 2%, respectively, and substance P (5 0 and 100 nM) dilated arterioles by only 6 +/- 2 and 5 +/- 3%, respect ively (p < 0.05 vs. nondiabetic hamsters). Nitroglycerin produced simi lar vasodilatation in nondiabetic and diabetic hamsters. Next, we exam ined whether exogenous application of L-arginine (100 mu M) could rest ore impaired histamine-and substance P-induced increases in arteriolar diameter in diabetic hamsters. We found that L-arginine did not resto re altered nitric oxide synthase-dependent vasodilatation in diabetic hamsters. These findings suggest that short-term diabetes mellitus alt ers agonist-induced increases in arteriolar diameter. In addition, the mechanism of altered arteriolar reactivity during diabetes mellitus d oes not appear to be related to an impaired availability of L-arginine .