title: ETa-receptor blockade, but not ACE inhibition, blunts retinal vessel response during isometric exercise.
abstract: Angiotensin II and endothelin-1 are potent vasoconstrictors that appear to play a role in retinal blood flow regulation. In the present study, we investigated the possible role of the angiotensin and the endothelin system in the regulation of retinal vessel diameters during isometric exercise in healthy humans. The study design was randomized, double-masked, placebo-controlled, and three-way cross over. Twelve healthy subjects performed squatting exercises for 6 min during infusion of either an angiotensin-converting enzyme inhibitor (enalapril), an ET(A)-receptor antagonist (BQ-123), or placebo. Retinal vessel diameters were measured continuously with the Zeiss retinal vessel analyzer. Systemic hemodynamics were assessed noninvasively, and intraocular pressure was measured with applanation tonometry. Squatting induced a significant increase in blood pressure and pulse rate, which was paralleled by a vasoconstriction in retinal arteries and veins. Intraocular pressure was only slightly increased during the squatting periods. BQ-123 significantly blunted the exercise-induced decrease in venous (P < 0.01) and arterial (P < 0.02, ANOVA) vessel diameters but had no effect on basal retinal diameters. By contrast, enalapril did neither influence vessel diameter at baseline conditions nor in response to isometric exercise. The data of the present study indicate that retinal vasoconstriction during isometric exercise is modified by ET(A)-receptor blockade, whereas it is not altered by angiotensin-converting enzyme inhibition. Hence, the present data indicate that endothelin-1, but not angiotensin II, is involved in retinal blood flow regulation during isometric exercise.
authors.affiliation: Dept. of Clinical Pharmacology, University of Vienna, A-1090 Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Luksch
authors.forename: Barbara
authors.initials: B
authors.lastname: Wimpissinger
authors.forename: Kaija
authors.initials: K
authors.lastname: Polak
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jandrasits
authors.forename: Leopold
authors.initials: L
authors.lastname: Schmetterer
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004656:Enalapril / Q000008:administration & dosage; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D005080:Exercise Test; D005260:Female; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010456:Peptides, Cyclic / Q000008:administration & dosage; D005082:Physical Exertion / Q000502:physiology; D015990:Placebo Effect; D044022:Receptor, Endothelin A / Q000378:metabolism*; D012171:Retinal Vessels / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D000804:Angiotensin II; D004656:Enalapril; C072247:cyclo(Trp-Asp-Pro-Val-Leu)