The ocular hemodynamic response to nitric oxide synthase inhibition is unaltered in patients with early type I diabetes.
BACKGROUND
An impaired ocular hemodynamic response to systemic nitric oxide synthesis inhibition has been demonstrated in patients with long-standing insulin-dependent diabetes mellitus. It is unclear whether this altered responsiveness is already detectable in early uncomplicated type I diabetes.


METHODS
The effect of the nitric oxide synthase inhibitor N(G)-monomethyl- l-arginine (L-NMMA) was studied in 10 male patients with early type I diabetes under euglycemic conditions and 10 healthy matched control subjects in a single (analyst) blinded cohort study design. Changes in ocular hemodynamics (fundus pulsation amplitude, mean flow velocity in the ophthalmic artery) and in pulse rate and mean blood pressure were measured in response to systemic intravenous doses of 1.5, 3, and 6 mg/kg L-NMMA.


RESULTS
L-NMMA dose-dependently and significantly decreased fundus pulsation amplitude (-21.0% vs -23.3% in diabetics and controls, respectively), mean flow velocity in the ophthalmic artery (-12.3% vs -10.8%) and pulse rate (-15.4% vs -16.6%) and increased mean arterial pressure (+19.5% vs +14.7%). The ocular and systemic hemodynamic effects of L-NMMA were not different between patients with diabetes and controls.


CONCLUSIONS
The responsiveness of the choroidal vasculature and the ophthalmic artery to L-NMMA is not altered in early type 1 diabetes. An impaired hemodynamic response to nitric oxide synthesis inhibition in diabetes is therefore not caused by a primary defect but rather due to altered vascular responsiveness secondary to long-standing disease.
Dorner
Guido T
GT
Department of Clinical Pharmacology, University of Vienna Medical School, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Garhöfer
Gerhard
G
Selenko
Nicole
N
Fasching
Peter
P
Bayerle-Eder
Michaela
M
Schmetterer
Leopold
L
Wolzt
Michael
M
D000328:Adult; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005123:Eye / Q000098:blood supply*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009880:Ophthalmic Artery / Q000503:physiopathology; D011674:Pulse; D016037:Single-Blind Method; D013997:Time Factors; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase