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 arteriolar diameter during diabetes mellitus. We used intravital microscopy to examine reactivity of cheek pouch arterioles (50 microns in diameter) in nondiabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. In nondiabetic hamsters histamine (1.0 and 5.0 microM) dilated cheek pouch arterioles by 15 +/- 1 and 22 +/- 1%, respectively, and substance P (50 and 100 nM) dilated arterioles by 14 +/- 3 and 21 +/- 4%, respectively. In addition, 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- and substance P-induced increases in arteriolar diameter were markedly reduced in diabetic hamsters. Histamine (1.0 and 5.0 microM) dilated arterioles by only 5 +/- 1 and 4 +/- 2%, respectively, and substance P (50 and 100 nM) dilated arterioles by only 6 +/- 2 and 5 +/- 3%, respectively (p < 0.05 vs. nondiabetic hamsters). Nitroglycerin produced similar vasodilatation in nondiabetic and diabetic hamsters. Next, we examined whether exogenous application of L-arginine (100 microM) could restore impaired histamine- and substance P-induced increases in arteriolar diameter in diabetic hamsters. We found that L-arginine did not restore altered nitric oxide synthase-dependent vasodilatation in diabetic hamsters. These findings suggest that short-term diabetes mellitus alters agonist-induced increases in arteriolar diameter. In addition, the mechanism of altered arteriolar reactivity during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
Patel
K P
KP
Sharpe
G M
GM
D000278:Administration, Buccal; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D004357:Drug Synergism; D008297:Male; D008647:Mesocricetus; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase