title: Role of endothelin-A receptors in optic nerve head red cell flux regulation during isometric exercise in healthy humans.
abstract: Endothelin-1 (ET-1) is an important regulator of vascular tone in the eye. It appears to play a role in ocular disease because of its strong vasoconstrictor action, its role in intraocular pressure homeostasis, and its neurotoxic potential. We have previously shown that ET-1 is involved in choroidal red cell flux (RCF) regulation during isometric exercise in healthy humans. In the present study we hypothesized that ET-1 also plays a role in optic nerve head (ONH) RCF regulation during isometric exercise. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, two-way crossover study in 15 healthy volunteers. Subjects were randomized to receive intravenous infusions of the specific endothelin type A receptor antagonist BQ-123 and placebo on two different study days. During these infusion periods, subjects performed squatting for 6 min to increase ocular perfusion pressure (OPP). ONH RCF was assessed with laser-Doppler flowmetry, and OPP was calculated from mean arterial pressure and intraocular pressure. BQ-123 did not change OPP or ONH RCF at baseline. The relative increase in OPP during isometric exercise was comparable between both groups (between 84 and 88%, P = 0.76 between groups; P < 0.001 vs. baseline). Isometric exercise increased ONH RCF during placebo and BQ-123, but the increase was more pronounced when the endothelin type-A receptor antagonist was administered (placebo, 27.3 ± 5.4%; and BQ-123, 39.2 ± 4.4%; P = 0.007 between groups). The present data indicate that ET-1 regulates red cell flux in the ONH beyond the autoregulatory range.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel 18-20,Vienna, Austria.
authors.forename: Agnes
authors.initials: A
authors.lastname: Boltz
authors.forename: Doreen
authors.initials: D
authors.lastname: Schmidl
authors.forename: René M
authors.initials: RM
authors.lastname: Werkmeister
authors.forename: Michael
authors.initials: M
authors.lastname: Lasta
authors.forename: Semira
authors.initials: S
authors.lastname: Kaya
authors.forename: Stefan
authors.initials: S
authors.lastname: Palkovits
authors.forename: Reinhard
authors.initials: R
authors.lastname: Told
authors.forename: Sophie
authors.initials: S
authors.lastname: Frantal
authors.forename: Gerhard
authors.initials: G
authors.lastname: Garhöfer
authors.forename: Leopold
authors.initials: L
authors.lastname: Schmetterer
mesh_terms: D000328:Adult; D062186:Arterial Pressure; D001317:Austria; D018592:Cross-Over Studies; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D015444:Exercise; D005260:Female; D006339:Heart Rate; D006801:Humans; D007262:Infusions, Intravenous; D007429:Intraocular Pressure; D007537:Isometric Contraction; D017078:Laser-Doppler Flowmetry; D008297:Male; D009898:Optic Disk / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000008:administration & dosage; D044022:Receptor, Endothelin A / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C072247:cyclo(Trp-Asp-Pro-Val-Leu)