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Originally published In Press as doi:10.1167/iovs.07-1399 on January 25, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:2557-2562.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1399
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Angiotensin (1-7) Reduces Intraocular Pressure in the Normotensive Rabbit Eye

Anu Vaajanen,1 Heikki Vapaatalo,1 Hannu Kautiainen,2 and Olli Oksala3

1From the Institute of Biomedicine, Pharmacology, University of Helsinki, Finland; the 2Rheumatism Foundation Hospital, Heinola, Finland; and the 3Research and Development Division, Santen Oy, Tampere, Finland.

PURPOSE. In the present study the effects of exogenous angiotensin II and its breakdown metabolite angiotensin (1-7) on the intraocular pressure (IOP) and on aqueous humor dynamics in normotensive rabbit eye were evaluated.

METHODS. Male New Zealand White rabbits with normal IOP were used for intravitreous and topical administration of the test compounds. IOP was measured in conscious rabbits by pneumatonometer after topical anesthesia. Outflow measurements were made with a two-level constant pressure method in anesthetized animals.

RESULTS. Angiotensin (1-7) administered intravitreously reduced IOP within 1 to 5 hours (P < 0.05). This effect was abolished by the selective angiotensin (1-7) antagonist A-779, and partially by the selective angiotensin II type 2 receptor antagonist PD123319. When olmesartan, an angiotensin II type 1 receptor blocker, was administered simultaneously with angiotensin (1-7), no antagonism was seen. Intravitreous administration of CGP42112 A, an angiotensin II type 2 receptor agonist, and angiotensin II did not significantly influence IOP, nor did topical administration of these compounds alter IOP. Angiotensin II significantly reduced outflow facility (P < 0.01) dose dependently, whereas angiotensin (1-7) had no effect.

CONCLUSIONS. Angiotensin (1-7) is a biologically active vasodilatory and antiproliferative heptapeptide, and its vascular effects counteract those of angiotensin II. It reduces intraocular pressure possibly by a selective Mas receptor, without changing aqueous humor outflow facility in the normotensive rabbit eye.






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