title: Mechanisms of angiotensin converting enzyme inhibitor-induced IOP reduction in normotensive rats.
abstract: Angiotensin converting enzyme inhibitors (ACEIs) have been shown to lower intraocular pressure (IOP). Since, the ACEIs cause increased tissue prostaglandin levels, we hypothesized that the mechanisms of ACEI-induced IOP reduction have similarity with those of prostaglandin analogs. The present study investigated the involvement of matrix metalloproteinases (MMPs) and cytokine activity modulation as the underlying mechanisms of ACEI-induced ocular hypotension. The IOP lowering effect of single drop of enalaprilat dehydrate 1% was evaluated in rats pretreated with a broad spectrum MMP inhibitor or a cytokine inhibitor. Effect of angiotensin receptor blocker, losartan potassium 2%, was also studied to evaluate involvement of angiotensin II receptor type 1 (AT1) in IOP lowering effect of ACEI. Topical treatment with single drop of enalaprilat resulted in significant IOP reduction in treated eye with mean peak reduction 20.3% at 3h post-instillation. Treatment with losartan resulted in a peak IOP reduction of 13.3%, which was significantly lower than enalaprilat, indicating involvement of mechanisms in addition to AT1 blockade. Pretreatment with a broad spectrum MMP inhibitor or a cytokine inhibitor significantly attenuated the enalprilat-induced IOP reduction with mean peak IOP reduction of 11.2% and 13.6% respectively. The IOP-lowering effect of enalaprilat seems to be attributed to reduced angiotensin II type 1 receptor stimulation and modulation of MMP and cytokines activities.
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000, Sungai Buloh, Selangor Darul Ehsan, Malaysia. Electronic address: renu@salam.uitm.edu.my.
authors.forename: Renu
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000, Sungai Buloh, Selangor Darul Ehsan, Malaysia. Electronic address: krasilnikova_ann@mail.ru.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Krasilnikova
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000, Sungai Buloh, Selangor Darul Ehsan, Malaysia.
authors.forename: Intan Safinaz
authors.initials: IS
authors.lastname: Raja
authors.affiliation: Department of Ophthalmology, IMU Clinical School, International Medical University, Seremban, Negeri Sembilan, Malaysia. Electronic address: puneet_agarwal63@yahoo.com.
authors.forename: Puneet
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Jalan Hospital, 47000, Sungai Buloh, Selangor Darul Ehsan, Malaysia. Electronic address: nafeeza@salam.uitm.edu.my.
authors.forename: Nafeeza
authors.initials: N
authors.lastname: Mohd Ismail
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D015237:Dinoprost; D020782:Matrix Metalloproteinases
keywords: Angiotensin II type 1 receptor blocker; Angiotensin converting enzyme inhibitor; Enalaprilat; Intraocular pressure; Matrix metalloproteinase; Tumor necrosis factor-alpha