Effect of the angiotensin-converting enzyme inhibitor zofenopril on nitric oxide metabolism in experimental glaucoma

Abstract

Glaucoma is an optic neuropathy, and nitric oxide ( NO) plays an important role as a modulator of autoregulation of blood circulation in the tissues of the optic nerve and retina. Much attention is paid to the role of NO me- tabolism disorders in the development of glaucoma. A new trend is the study of angiotensin-converting enzyme ( ACE) inhibitors as potential anti- glaucomatous agents. Purpose: To study the features of N O metabolism in eye tissues during glaucoma modelling and the use of the ACE inhibitor zofenopril ( ZP). Material and Methods: Adrenaline-induced glaucoma ( AIG) was mod- elled in rabbits by intravenous administration of 0.1 ml of adrenaline solu- tion (1.80 mg/ml) for 3 months (40 injections). Some animals during AIG simulation received zofenopril ( ZP) per os in the form of 1 ml of aqueous suspension (1 mg/kg body weight). The condition of the animals’ eyes was monitored ophthalmoscopically and biomicroscopically. Signs of primary glaucoma with increased intraocular pressure (I OP) were formed in AIG. In the tissues of the eye drainage zone, retina and optic nerve of animals, indicators of N O metabolism were determined: the level of stable N O metabolites (nitrate (NOˉ 3) and nitrite (NOˉ2) anions) and the total activity of constitutive neuronal and endothelial NO- synthases (cNO-synthase). Results: In AIG, a significant decrease in the level of NOˉ3 and NOˉ2 an- ions and the activity of cNO-synthases was found in the tissues of the rabbit eye. The use of ZP in AIG contributed to an increase in the level of NOˉ3-anions in the tissues of the drainage zone by 28.2 %, in the retina by 20.5 %, in the optic nerve of animals by 18.2 %, NOˉ2-anions by 43.0 %, 31.5 % and 22.8 % (p < 0.05), respectively, compared with the data of A IG without treatment. The introduction of Z P suspension against the back- ground of A IG in animals contributed to a significant activation of cNO- synthases in the tissues of the drainage zone by 38.7 %, in the retina by 35.8 % and in the optic nerve by 30.6 % compared to animals with A IG without treatment. Conclusion: The study on AIG show a positive effect of ZP on pathoge- netic links of N O metabolism, which contributed to the reduction of IOP. The obtained experimental data may be a preclinical justification for the feasibility of using zofenopril in the complex therapy of glaucoma in clini- cal conditions.