Nitric oxide and ocular blood flow in patients with IDDM.
Endothelial dysfunction has been implicated in the pathogenesis of diabetic vascular disorders such as diabetic retinopathy. We hypothesized that either local endogenous nitric oxide (NO) synthesis or local reactivity to endogenous NO might be impaired in patients with IDDM and that this may contribute to the development of diabetic retinopathy. Ten otherwise healthy patients with long-standing IDDM and ten healthy control subjects were studied according to an open randomized two-way cross-over design. Subjects received intravenous infusions of either N(G)-monomethyl-L-arginine, an inhibitor of NO-synthase, or L-arginine, the precursor of NO synthesis, on two separate study days. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine decreased fundus pulsations and blood flow velocity in the ophthalmic artery and increased blood pressure in healthy subjects. The responses to NO-synthase inhibition were significantly less in diabetic subjects. In contrast, L-arginine caused a comparable increase in fundus pulsations and decrease in blood pressure in both cohorts. These results indicate that systemic and ocular hemodynamic reactivity to NO-synthase inhibition is reduced in patients with long-standing IDDM, compared with healthy control subjects. Thus, this study indicates that either NO-synthase activity is increased or NO sensitivity is decreased in patients with IDDM and supports the concept of an involvement of the L-arginine-NO system in the pathophysiology of diabetic retinopathy.
Schmetterer
L
L
Department of Clinical Pharmacology, Vienna University School of Medicine, Austria.
Findl
O
O
Fasching
P
P
Ferber
W
W
Strenn
K
K
Breiteneder
H
H
Adam
H
H
Eichler
H G
HG
Wolzt
M
M
D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000209:etiology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005123:Eye / Q000098:blood supply* / Q000187:drug effects; D006439:Hemodynamics; D006801:Humans; D007262:Infusions, Intravenous; D007834:Lasers; D008297:Male; D008857:Microscopy, Interference; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009880:Ophthalmic Artery / Q000187:drug effects / Q000503:physiopathology*; D011673:Pulsatile Flow / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase