IOVS Circulation
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mori, F.
Right arrow Articles by Bursell, S.-E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mori, F.
Right arrow Articles by Bursell, S.-E.
(Investigative Ophthalmology and Visual Science. 2000;41:3955-3962.)
© 2000 by The Association for Research in Vision and Ophthalmology, Inc.

Endothelin-3 Regulation of Retinal Hemodynamics in Nondiabetic and Diabetic Rats

Fumihiko Mori, George L. King, Allen C. Clermont, Dahlia K. Bursell and Sven-Erik Bursell

From the Research Division and Beetham Eye Institute, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.

PURPOSE. To investigate the mechanisms of action of endothelin (ET)-3 on the regulation of retinal hemodynamics in diabetic and nondiabetic rats.

METHODS. Retinal blood flow changes were measured using video fluorescein angiography. Measurements were made before and after intravitreal injections of different ET-3 concentrations in nondiabetic rats and rats with streptozotocin (STZ)-induced diabetes. The effect of ET-3 on retinal blood flow was also investigated in nondiabetic rats after pretreatment with NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (NOS) inhibitor; BQ-788, an ET receptor B (ETB) antagonist; and BQ-123, an ET receptor A (ETA) antagonist. Control animals were injected intravitreally with vehicle alone.

RESULTS. In nondiabetic rats, ET-3 induced a dose-dependent rapid increase in retinal blood flow 2 minutes after intravitreal injection (maximal at 10-8 M, P < 0.01) followed 15 and 30 minutes after ET-3 injection by dose-dependent decreases in retinal blood flow (maximal effect at 10-6 M, P < 0.05). The ET-3–stimulated retinal blood flow increase was inhibited by 10-4 M BQ-788 (P < 0.01) and 10-3 M L-NMMA (P < 0.05). The ET-3–stimulated decrease in retinal blood flow at later times (15 minutes) was inhibited (P < 0.03) by 10-4 M BQ-123. In diabetic rats, baseline retinal blood flows were decreased compared with nondiabetic rats (P < 0.01), showed dose-dependent increases 2 minutes after ET-3 injection (P < 0.03), and at later times remained significantly increased (P < 0.05) in contrast to flows in nondiabetic rats.

CONCLUSIONS. The ET-3–induced initial rapid retinal blood flow increase in nondiabetic rats is mediated by the ET-3/ETB and NOS action. The subsequent retinal blood flow decrease is mediated by ET-3/ETA action. Diabetic rats showed comparable ET-3–induced retinal blood flow increases indicating normal ET-3/ETB action. However, at later times, retinal blood flow remained increased, suggesting an abnormal ET-3/ETA action.




This article has been cited by other articles:


Home page
 IOVSHome page
X. Zhang, A. F. Clark, and T. Yorio
Interactions of Endothelin-1 with Dexamethasone in Primary Cultured Human Trabecular Meshwork Cells
Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5301 - 5308.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by the Association for Research in Vision and Ophthalmology