Effects of adrenomedullin on ocular hemodynamic parameters in the choroid and the ophthalmic artery.
OBJECTIVE
Adrenomedullin acts as a vasodilator and may play a role in inflammatory processes in the eye. This study was designed to determine whether nitric oxide formation is involved in the response to adrenomedullin in the ocular vasculature in vivo.


METHODS
The effects of systemic intravenous adrenomedullin (3.2-16.0 pmol/[kg. min])) on choroidal blood flow were assessed by measurement of fundus pulsation amplitude and laser Doppler flow in the macula, and on blood flow in the ophthalmic artery by ultrasound Doppler flow in pilot studies (n = 7). Subsequently, in a double-blind randomized placebo-controlled crossover study in eight healthy male subjects the effects of 12.8 pmol/(kg. min) adrenomedullin on ocular and systemic hemodynamics were investigated. Adrenomedullin was co-infused with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (3 mg/kg bolus and 30 micro g/[kg. min] continuous intravenous infusion) or vehicle control on separate study days.


RESULTS
Adrenomedullin dose dependently increased choroidal blood flow and flow velocity in the ophthalmic artery. N(G)-monomethyl-L-arginine reduced the effect of adrenomedullin on fundus pulsation amplitude, but did not alter the flow response in the ophthalmic artery. Systemic hemodynamics were unaffected by adrenomedullin infusion.


CONCLUSIONS
Ocular blood flow is sensitive to changes in adrenomedullin concentrations. The acute vasodilator effects of adrenomedullin are nitric oxide-dependent in the choroid, but not in the ophthalmic artery.
Dorner
Guido T
GT
Department of Clinical Pharmacology, Allgemeines Krankenhaus Vienna, Vienna, Austria.
Garhöfer
Gerhard
G
Huemer
Karl-Heinz
KH
Golestani
Elisabeth
E
Zawinka
Claudia
C
Schmetterer
Leopold
L
Wolzt
Michael
M
D053607:Adrenomedullin; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000502:physiology; D002829:Choroid / Q000098:blood supply*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005123:Eye / Q000098:blood supply*; D006439:Hemodynamics; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D009880:Ophthalmic Artery / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology*; D010865:Pilot Projects; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide