Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans.
OBJECTIVE
There is evidence that the choroid has some autoregulatory capacity in response to changes in ocular perfusion pressure (OPP). The mediators of this response are hitherto unidentified. The hypothesis for the current study was that endothelin (ET)-1 and/or angiotensin (ANF)-II may be involved in choroidal vasoconstriction during an increase in OPP.


METHODS
To test this hypothesis a randomized, double-masked, placebo-controlled, three way crossover study was performed in 12 healthy male volunteers. Subjects received on different study days intravenous infusions of the specific ET(A) receptor antagonist BQ-123, the angiotensin converting enzyme inhibitor enalapril or placebo. During these infusion periods subjects were asked to squat for 6 minutes. Choroidal blood flow was measured using a confocal laser Doppler flowmeter and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure.


RESULTS
BQ-123 and enalapril had no effect on basal blood pressure, pulse rate, intraocular pressure, or choroidal blood flow. During isometric exercise, a pronounced increase in mean arterial pressure paralleled by an increase in OPP was observed. Although choroidal blood flow slightly increased during squatting, the increase was much less pronounced than the increase in OPP, indicating some regulatory potential of the choroid. Enalapril did not alter the choroidal pressure-flow relationship during isometric exercise, but BQ-123 induced a significant leftward shift of the pressure-flow curve (P < 0.001).


CONCLUSIONS
The present data indicate that ET-1, but not ANG II, plays a role in choroidal blood flow regulation during isometric exercise in healthy humans. Hence, impaired choroidal autoregulation in patients with ocular vascular diseases may arise from an altered endothelin system. Further studies in such patients are warranted to verify this hypothesis.
Fuchsjäger-Mayrl
Gabriele
G
Department of Clinical Pharmacology, University of Vienna, Vienna, Austria.
Luksch
Alexandra
A
Malec
Magdalena
M
Polska
Elzbieta
E
Wolzt
Michael
M
Schmetterer
Leopold
L
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002829:Choroid / Q000098:blood supply*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004656:Enalapril / Q000494:pharmacology; D010450:Endopeptidases / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D015444:Exercise / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007429:Intraocular Pressure / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D044022:Receptor, Endothelin A
D000806:Angiotensin-Converting Enzyme Inhibitors; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D004656:Enalapril; D010450:Endopeptidases; C047491:angiotensin-producing serum enzyme II; C072247:cyclo(Trp-Asp-Pro-Val-Leu)