Reversal by L-arginine of a dysfunctional arginine/nitric oxide pathway in the endothelium of the genetic diabetic BB rat.
We examined the effects of acute supplementation with arginine in vitro on endothelium-dependent relaxation in aortic rings taken from female genetic, diabetes-prone BB rats. Sensitivity to norepinephrine-induced contraction was unaltered in rings of diabetic BB rats compared to rings from non-diabetic littermates. In precontracted rings, acetylcholine produced a concentration-dependent relaxation which was impaired by diabetes. This relaxation was blocked by L-nitroarginine in both control and diabetic rings. Addition of 3 mmol/l L-arginine (but not D-arginine) enhanced relaxation in diabetic rings similar to that seen in control rings without arginine. L-arginine had no effect on acetylcholine-induced relaxation in control rings. In contrast, relaxation-induced by nitroglycerin in diabetic rings without endothelium was not altered by L-arginine treatment. Thus, a defect in the utilization of arginine by nitric oxide synthase exists in the endothelium of the diabetic BB rat.
Pieper
G M
GM
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
Siebeneich
W
W
Moore-Hilton
G
G
Roza
A M
AM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D005260:Female; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D051381:Rats; D011913:Rats, Inbred BB
D001120:Arginine; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D000109:Acetylcholine