Return to search

Influ?ncia de f?rmacos no sistema-renina-angiotensina do globo ocular de c?es h?gidos: desenvolvimento farmacot?cnico e avalia??o cl?nica / Influence of drugs on the renin-angiotensin system of the ocular globe of healthy dogs: pharmacotechnical development and clinical evaluation

Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2017-01-24T16:23:42Z
No. of bitstreams: 1
2015 - Eriane de Lima Caminotto.pdf: 1339748 bytes, checksum: 753de2c181b04ca05748c103c2d6ec8b (MD5) / Made available in DSpace on 2017-01-24T16:23:42Z (GMT). No. of bitstreams: 1
2015 - Eriane de Lima Caminotto.pdf: 1339748 bytes, checksum: 753de2c181b04ca05748c103c2d6ec8b (MD5)
Previous issue date: 2015-10-21 / Funda??o Carlos Chagas Filho de Amparo ? Pesquisa do Estado do RJ - FAPERJ / Glaucoma is a disease that causes more blindness in dogs and has no cure, only treatment. The difficulty in the drainage of aqueous humor (AH) results in an increase in intraocular pressure (IOP), representing a significant risk factor for the occurrence of this condition, leading to irreversible damage to the progressive loss of visual field and vision as a whole death of retinal ganglion cells (RGC), loss of axons in the optic nerve and excavation of the same. In addition to this, several mechanisms may contribute to the development and progression of this disease, for example, unbalances of the renin-angiotensin-system (RAS), and cardiovascular and renal diseases. The measurement of IOP and the examination of the fundus are the methods used to diagnose this condition. The treatment of choice is based on eye drops that stimulate drainage of HA and / or decrease their production resulting in IOP control; however in many cases the treatment does not attain the desired effect, culminating in blindness. In an attempt to change this therapeutic perspective, this study compared, in healthy and normotensive Beagle dogs, systemic and ocular action of three drugs: timolol maleate 0.5% (non-selective beta-blocker used in cases of glaucoma) , captopril 0.1% and 0.5% (ECA1 inhibitor never before studied in greater concentration in dogs) and aceturato of diminazene - DIZE 0.1% and 0.5% (endogenous activator of ACE2, never before researched in eyes canines). The latter two drugs were formulated for ophthalmic use for the reduction of IOP, since it is known about the existence of SARS eye level, and that they have been successfully administered systemically at reducing systemic arterial pressure (SAP). Thus, before and after treatment, 18 dogs underwent the Schirmer Tear Test (TLS1) and blood collection for measuring the concentration of angiotensin-converting enzyme (ECA1) serum. For three consecutive days before treatment and at three times (6h, 12h and 18h) all animals have gone through four exams, always following the same order: evaluation of pupil size, IOP measurement, measurement of HR and SAP. After obtaining the normal range, the animals had the left eye subjected to predetermined protocols initially with 1 drop every 12 hours, 7 days a lower concentration and, in the other seven days, in the highest concentration. The adelfos eyes were control and every day in the three different times dogs went through the same initial exams. All drugs were good penetration and no adverse eye level. As for tear production, captopril is the most suitable for glaucoma patients and patients with keratoconjunctivitis sicca, while timolol is contraindicated for them. All decreased IOP values, and in the second week of treatment, with higher concentrations, reductions were more significant. The bradycardia was observed in captopril-treated animals 0.5%, with a reduction of almost 9% in HR compared to captopril in lower concentrations / O glaucoma ? uma das doen?as que mais causa cegueira em c?es e n?o possui cura, apenas tratamento. A dificuldade na drenagem do humor aquoso (HA) resulta no aumento da press?o intra-ocular (PIO) que representa um fator de risco significativo para a ocorr?ncia dessa afec??o, conduzindo ? danos irrevers?veis como a perda progressiva do campo visual e da vis?o como um todo, morte das c?lulas ganglionares da retina (CGR), perda de ax?nios do nervo ?ptico e escava??o do mesmo. Al?m deste, diversos mecanismos podem contribuir para o desenvolvimento e progress?o desta doen?a como, por exemplo, os desequil?brios do sistema-renina-angiotensina (SRA) e as doen?as cardiovasculares e renais. A mensura??o da PIO e o exame do fundo de olho s?o os m?todos mais utilizados para diagnosticar essa afec??o. O tratamento de escolha se baseia em col?rios que estimulam a drenagem do HA e/ou diminuam sua produ??o resultando no controle da PIO; por?m em muitos casos a terapia n?o atinge o efeito desejado e culmina em cegueira. Na tentativa de mudar essa perspectiva terap?utica, o presente trabalho comparou, em c?es sadios e normotensos da ra?a Beagle, a a??o sist?mica e ocular de tr?s f?rmacos: maleato de timolol 0,5% (beta-bloqueador n?o seletivo usado nos casos de glaucoma), captopril 0,1% e 0,5% (inibidor de ECA1 nunca antes estudado nesta maior concentra??o em c?es) e aceturato de diminazeno ? DIZE 0,1% e 0,5% (ativador end?geno de ECA2, nunca antes pesquisado em olhos caninos). Os dois ?ltimos f?rmacos foram formulados para uso oftalmol?gico visando a redu??o da PIO, uma vez que ? sabido sobre a exist?ncia do SRA a n?vel ocular e que os mesmos j? foram administrados sistemicamente com sucesso na redu??o press?o arterial sist?mica (PAS). Dessa forma, antes e ap?s os tratamentos, 18 c?es foram submetidos ao teste lacrimal de Schirmer (TLS1) e ? coleta sangu?nea para dosagem da concentra??o da enzima conversora de angiotensina (ECA 1) do soro.Durante tr?s dias consecutivos antes dos tratamentos e em tr?s hor?rios distintos (6h, 12h, e 18h) todos os animaispassaram por quatro exames, seguindo sempre a mesma ordem: avalia??o do di?metro pupilar, aferi??o da PIO, aferi??o da FC e da PAS.Ap?s a obten??o dos valores normais, os animais tiveram o olho esquerdo submetido aos protocolos pr?-determinados inicialmente com 1 gota, a cada 12 horas, por 7 dias na menor concentra??o e, nos demais 7 dias, na maior concentra??o. Os olhos adelfos foram o controle e, todos os dias nos tr?s hor?rios distintos os c?es passaram pelos mesmos exames iniciais. Todos os f?rmacos tiveram boa penetrabilidade e aus?ncia de efeitos adversos a n?vel ocular. Quanto ? produ??o lacrimal, o captopril ? o mais indicado para os pacientes glaucomatosos e portadores de ceratoconjuntivite seca, enquanto que o timolol ? contra-indicado para os mesmos. Todos diminu?ram os valores da PIO, sendo que na segunda semana de tratamento, com concentra??es maiores, as redu??es foram mais significativas. A bradicardia foi observada nos animais tratados com captopril 0,5%, com uma redu??o de quase 9% na FC, quando comparado com o captopril em menor concentra??o.

Identiferoai:union.ndltd.org:IBICT/oai:localhost:jspui/1390
Date21 October 2015
CreatorsCaminotto, Eriane de Lima
ContributorsReis, Luis Carlos, Pigatto, Jo?o Antonio Tadeu, Fonseca, Fabr?cia Viana, C?rtes, Wellington da Silva, Paiva, Jonimar Pereira
PublisherUniversidade Federal Rural do Rio de Janeiro, Programa de P?s-Gradua??o em Medicina Veterin?ria (Patologia e Ci?ncias Cl?nicas), UFRRJ, Brasil, Instituto de Veterin?ria
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis
Formatapplication/pdf
Sourcereponame:Biblioteca Digital de Teses e Dissertações da UFRRJ, instname:Universidade Federal Rural do Rio de Janeiro, instacron:UFRRJ
Rightsinfo:eu-repo/semantics/openAccess
Relation8 REFER?NCIAS BIBLIOGR?FICAS ABRAMS, K.L. Medical and surgical management of the glaucoma patient. Clinical Technical Small Animal Practice, v.16, p.71-76, 2001. ABRAMS, K.L.; BROOKS, D.E.; LARATTA, L.J.; BARNHILL, M.A.; FRAZIER, D. Angiotensin converting enzyme system in the normal canine eye: pharmacological and physiological aspects. Journal of Ocular Pharmacology and Therapeutics, v.1, p. 41-51, 1991. ADAMS, H.R. Farmacologia e Terap?utica em Veterin?ria. 8 ed. Rio de Janeiro: Guanabara&Koogan, 2001. 1034 p. AGUILERA, G; KISS A. Regulation of the hypothalamic-pituitary-adrenal axis and vasopressin secretion. Role of angiotensin II. Advances in Experimental Medicine and Biology, v.396, p.105?12, 1996. BATISTUZZO, J.A.O.; ETO, Y.; ITAYA, M. Formul?rio M?dico Farmac?utico. 4 ed. Editora Pharmabooks, 2011. 65-76p. BERKA, J.L.; STUBBS, A.J.; WANG, D.Z. Renin-containing M?ller cells of the retina display endocrine features. Investigative Ophthalmology & Visual Science, v.36, p.1450?1458, 1995. BONOMI, L.; ZAVARISE, G.; NOYA, E.; MICHIELETTO, S. Effects of timolol maleate on tear flow in human eyes. Albrecht Von Graefes Arch Klin Exp Ophthalmol. v.1, p.19-22, 1980. BOROVIC, D.; BENDELIC, E.; CHISELI??, D. Study of kini-kallikrein and renin-angiotensin systems in patients with primary open angle glaucoma. Oftalmologia, v.53, n.2, p.61-68, 2009. BROOKS, D.E.; GARCIA, G.A.; DREYER, E.B.; ZURAKOWSKI, D.; FRANCO-BOURLAND, R.E. Vitreous body glutamate concentration in dogs with glaucoma. American Journal of Veterinary Research, v.58, p.864-867, 1997. CABRAL, R.R.; CIASCA, B.D.; OLIVEIRA, V.M.C.; VAZ-CURADO, A.P.; LARSSON, M.H.M.A. Valores da press?o arterial em c?es pelos m?todos oscilom?trico e Doppler vascular. Arquivo Brasileiro de Medicina Veterin?ria e Zootecnia, v.62, n.1, 2010. CHIOU, H.J. et al. Evaluation of ocular arterial changes in glaucoma with color Doppler ultrasonography. Journal Ultrasound in Medicine, v.18, p.295-302, 1999. CONSTAD, W.H.; FIORE, P.; SAMSON, C.; CINOTTI, A.A. Use of an angiotensin converting enzyme inhibitor in ocular hypertension and primary open-angle glaucoma. American Journal of Ophthalmology, v.105, p.674-677, 1988. 40 CRAWFORD, K.; KAUFMAN, P.L. Pilocarpine antagonizes prostaglandin F2?-induced ocular hypotension in monkeys. Evidence for enhancement of Uveoscleral outflow by prostaglandin F2?. Archives of ophthalmology, v.105, p.1112?1116, 1987. CULMAN, J.; HOHLE, S.; QADRI, F.; EDLING, O.; BLUME, A.; LEBRUN, C.; UNGER, T. Angiotensin as neuromodulator/neurotransmitter in central control of body fluid and electrolyte homeostasis. Clinical and Experimental Hypertension, v.17, p.281?293, 1995. CUNHA-VAZ, J. The blood-ocular barriers. Survey of Ophthalmology, v.23, p.279?296, 1979. CUNHA-VAZ, J.G. The blood-retinal barrier system. Basic concepts and clinical evaluation. Experimental Eye Research, v.78, p.715-721, 2004. DANSER, A.H.J.; DERKX, F.H.M.; ADMIRAAL, P.J.J.; DEINUM, J.; DE JONG, P.T.V.M.; SCHALEKAMP, M.A.D.H. Angiotensin levels in the eye. Investigative Ophthalmology & Visual Science, v.35, p.:1008?1018, 1994. DE GASPARO, M.; CATT, K.J.; INAGAMI, T.; WRIGHT, J.W.; UNGER, T. International union of pharmacology XXIII. The angiotensin II receptors. Pharmacology Reviews, v.52, p.415-472, 2000. DYCE, K. M.; WENSING, C. J. G.; SACK, W. O. Tratado de Anatomia Veterin?ria. 3 ed. S?o Paulo: Elsevier Brasil, 2004. 813 p. DONOGHUE, M.; HSIEH, F.; BARONAS, E.; GODBOUT, K.; GOSSELIN, M.; STAGLIANO, N.; DONOVAN, M.; WOOLF, B.; ROBISON, K.; JEYASEELAN, R.; BREITBART, R.E.; ACTON, S. A novel angiotensin-converting enzymerelated carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circulation research. v.87, p.1-9, 2000. FELDMAN, R.M. Conjuntival hyperemia and the use of topical prostaglandins in glaucoma and ocular hypertension. Journal of Ocular Pharmacology and Therapeutics, New York, v.19, n.1, p.23-31, 2003. FOUREAUX, G.; NOGUEIRA, J.C.; NOGUEIRA, B.S.; FULG?NCIO, G.O.; MENEZES, G.B.; FERNANDES, S.O.; CARDOSO, V.N.; FERNANDES, R.S.; OLIVEIRA, G.P.; FRANCA, J.R.; FARACO, A.A.; RAIZADA, M.K.; FERREIRA, A.J. Antiglaucomatous effects of the activation of intrinsic Angiotensin-converting enzyme 2. Investigative Ophthalmology & Visual Science, v.6, p.4296-4306, 2015. GELATT, K.N.; BROOKS, D.E. The canine glaucomas. In:______. Veterinary ophthalmology. 3.ed. Malvern: Lea & Febiger, cap.21, p.701-754, 1999. GIESE, M.J.; SPETH, R.C. The ocular renin?angiotensin system: A therapeutic target for the treatment of ocular disease. Pharmacology & Therapeutics. p.1-22, 2013. 41 GIONFRIDDO, J.R. Recognizing and managing acute and chronic cases of glaucoma. Veterinary Medicine, v.90, p.265-275, 1995. GOODMAN & GILMAN. As bases farmacol?gicas da terap?utica. 12. ed. Porto Alegre: AMGH, 2012. 2112 p. GYTON, A.C.; HALL, J.E. Tratado de Fisiolog?a M?dica. 10 ed. McGraw-Hill Interamericana de Espa?a, 2001. 695-699 p. HAKANSON, N.; DRU FORRESTER, S. Uveitis in the dog and cat. Veterinary Clinics of North America Small Animal Practice, v.20, n.3, p.715-735, 1990. HIROOKA, K.; SHIRAGA, F. Potential role for angiotensin-converting enzyme inhibitors in the treatment of glaucoma. Clinical Ophthalmology. v.3, p. 217?223, 2007. HOY, Y.; DELAMERE, N.A. Influence of ANG II on cytoplasmic sodium in cultured rabbit nonpigmented ciliary epithelium. American Journal of Physiology - Cell Physiology, v.283, p.552?559, 2002. IUSUF, D.; HENNING, R.H.; VAN GILST, W.H.; ROKS, A.J. Angiotensin-(1-7): Pharmacological properties and pharmacotherapeutic perspectives. European Journal of Pharmacology. v.13, p.303-312, 2008. ITO, M.; OLIVERIO, M.I.; MANNON, P.J. Regulation of blood pressure by the type 1A angiotensin II receptor gene. Proceedings of the National Academy of Sciences of the United States of America, v.92, p.3521?3525, 1995. JACKSON, K.E. Renin and Angiotensin. In: Goodman & Gilman`s The pharmacological basis of therapeutics. 11 ed. New York: Medical Publishing Division, 2006. 789-814p. JEGOU, J.P. L?s glaucomes. Recueil de M?decine V?t?rinaire, v.165, p.263-278, 1989. KAZUYUKI, H.; FUMIO, S. Potential role for angiotensin-converting enzyme inhibitors in the treatment of glaucoma. Clinical Ophthalmology, v.3, p.217-223, 2007. KHAN, N.; KHALEQUE, M.A.; ISLAM, M.S.; BEGUM, R.A.; UDDIN, M.S.; HOSSAIN, M.M.; ALI M. Effect of topical Beta blocker (Timolol maleate 0.5%) in primary open angle glaucoma. Mymensingh Medical Journal, v.4, p.648-653, 2012. KOSTENIS, E.; MILLIGAN, G.; CHRISTOPOULOS, A.; SANCHEZ-FERRER, C.F.; HERINGER-WALTHER, S.; SEXTON, P.M.; GEMBARDT, F.; KELLETT, E.; MARTINI, L.; VANDERHEYDEN, P.; SCHULTHEISS, H.P.; WALTHER, T. G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor. Circulation, v.14, p.1806-1813, 2005. KUNER, A.; VIEIRA, J.B.; CAVALCANTI, P.D.C.; FALEIRO, R.D. Retrospective study (2010-2013) of the incidence of keratoconjunctivitis sicca (KCS) in dogs with glaucoma. Veterinary Ophthalmology, v.16, p.4121-425, 2013. 42 KWON, Y.H.; CAPRIOLI, J. Primary open angle glaucoma. In: Duane`s Ophthalmology. CD-ROM ed. Lippincot Williams et Wilkins, 2006, v.3, 45p. LEMOS, V.S.; SILVA, D.M.; WALTHER, T.; ALENINA, N.; BADER, M.; SANTOS, R.A. The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of masknockout mice. Journal Cardiovascular Pharmacology, v. 46, p. 274-279, 2005. LUHTALA, S.; VAAJANEN, A.; OKSALA, O.; VALJAKKA, J.; VAPAATALO, H. Activities of angiotensin-converting enzymes ACE1 and ACE2 and inhibition by bioactive peptides in porcine ocular tissues. Journal of Ocular Pharmacology and Therapeutics, v.25, n.1, p.23-28, 2009. MALEATO DE TIMOLOL. Respons?vel t?cnico Elizabeth Mesquita. S?o Paulo: Allergan Produtos Farmac?uticos LTDA, 2013. Bula de rem?dio. MARTINS, B.C.; VICENTI, F.A.M.; LAUS, J.L. S?ndrome glaucomatosa em c?es ? Parte 1. Ci?ncia Rural, v.36, n.6, 2006. MEHTA, A.; IYER, L.; PARMAR, S.; SHAH, G.; GOYAL, R. Oculohypotensive effect of perindopril in acute and chronic models of glaucoma in rabbits. Canadian Journal of Physiology and Pharmacology, v.88, n.5, p.595-600, 2010. MITCHELL, P.; LEE, A.J.; ROCHTCINA, E.; WANG, J.J. Open-angle glaucoma and systemic hypertension: The Blue Mountains Eye Study. Journal Glaucoma, v.13, p.319-326, 2004. MU?OZ-NEGRETE, F.J.; P?REZ-L?PEZ, M.; WON KIM, H.R.; REBOLLEDA, G. Nuevos desarrollos en el tratamiento m?dico del glaucoma. Archivos de la Sociedad Espa?ola de Oftalmolog?a, n.10, v.84, p.491-500, 2009. NASKAR, R.; DREYER, E. New horizons in neuroprotection. Survey of Ophthalmology, v.5, supl.3, p.S250-S255, 2001. ORI?, A. P. Considerations abaout etectroretinography in dogs. Ci?ncia Rural, v. 34, p. 323-328, 2004. PLUMMER, C.E.; MACKAY, E.O.; GELATT, K.N. Comparison of the effects of topical administration of a fixed combination of dorzolamide-timolol to monotherapy with timolol or dorzolamide on IOP, pupil size, and heart rate in glaucomatous dogs. Veterinary Ophthalmology. v.9, n.4, p.245-249, 2006. PRATT, N.L.; RAMSAY, E.N.; ELLETT, L.M.K.; NGUYEN, T.A.; ROUGHEAD, E.E. Association between Ophthalmic Timolol and Hospitalisation for Bradycardia. Journal of Ophthalmology, p.387-393, 2015. QUIROZ Mercado, Joaqu?n, Curso De Actualizaci?n En Oftalmolog?a Em Perros Y Gatos, Universidad Michoacana de San Nicol?s de Hidalgo, M?xico, 2007. 43 RAMIREZ, M.; DAVIDSON, E.A.; LUTTENAUER, L.; ELENA, P.P.; CUMIN, F.; MATHIS, G.A.; DE GASPARO, M. The renin-angiotensin system in the rabbit eye. Journal of Ocular Pharmacology and Therapeutics, v.12, n.3, p.299-312, 1996. REINSTEIN, S.L.; RANKIN, A.J.; ALLBAUGH, R. Canine glaucoma: phatophysiology and diagnosis. Compendium: Continuing Education for Vetinarians. v.31, n.10, p.450-452, 2009. RIBEIRO, A.P.; MARTINS, B.C.; LAUS, J.L. S?ndrome glaucomatosa em c?es ? parte 2. Ci?ncia. Rural, v.37, n.6, 2007. ROBINSON, C.C.; ALLBAUGH, R.A.; RAMIREZ, A.; JEANS, J.K.; WHITLEY, R.D.; BEN-SHLOMO, G.; ELLINWOOD, N.M. The effect of topical 0,5% timolol maleate ophthalmic solutionon canine tears. Veterinary Ophthalmology, v.16, p.413-416, 2013. SAGARA, T. ; GATON, D.D. ; LINDSEY, J.D. ; GABELT, B.T. ; KAUFMAN, P.L. ; WEINREB, R.N. Topical prostaglandin F2alpha treatment reduces collagen types I,II,II and IV in the monkey uveoscleral outflow pathway. Archives of Ophthalmology, Chicago, v.117, n.6, p.794-801, 1999. SANTOS, R.A.; SIMOES E SILVA, A.C.; MARIC, C.; SILVA, D.M.; MACHADO, R.P.; DE BUHR, I. Angiotensin (1-7) is an endogenous ligand for the G-protein-coupled receptor Mas. Proceedings of the National Academy of Sciences of the United States of America, v.8, p.8258-8263, 2003. SLATTER, D. Glaucoma. In:______. Fundamentals of veterinary ophthalmology. 2.ed. Philadelphia:Saunders, p.338-364, 1990. SLATTER, D. Fundamentos De Oftalmolog?a Veterinaria, 3? Edici?n, Editorial. Inter-M?dica, Buenos Aires, Argentina, p. 390-450, 2004. SLATTER, D. Tratado de Cirug?a en peque?os animales, Tercera Edici?n, Tomo 2, Editorial Inter-M?dica, Argentina, p. 1671-1697, 2005. SOLTAU, J.B.; ZIMMERMAN, T.J. Changing paradigms in the medical treatment of glaucoma. Survey in Ophthalmology, New York, v.47, Suppl 1, p.s2-5, 2002. SU, J.B. Kinins and cardiovascular diseases. Current Pharmceutical Design, v.12, p.3423-3435, 2006. TAKIYAMA, N.; SHOJI, S.; HABATA, I.; OHBA, S. The effects of a timolol maleate gel-forming solution on normotensive Beagle dogs. Journal of Veterinary Medical Science, v.6, p.631-633, 2006. TAMBURRELLI, C. Ultrasonographic evaluation of optic disc swelling: comparison with cslo in idiopathic intracranial hypertension. Investigative Ophthalmology & Visual Science, v.41, p.2960?2966, 2000. 44 TIELSCH, J.M.; KATZ, J.; SOMMER, A.; QUIQLEY, H.A.; JAVITT, J.C. Hypertension, perfusion pressure, and primary open angle glaucoma. A population-based assessment. Archives of Ophthalmology. v.113, p.216-221, 1995. TIKELLIS, C.; BERNARDI, S.; BURNS, W.C. Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal disease. Current Opinion in Nephrology and Hypertension, v.1, p.62-68, 2011. VAAJANEN, A.; VAPAATALO, H.; KAUTIAINEN, H.; OKSALA, O. Angiotensin (1-7) reduces intraocular pressure in the normotensive rabbit eye. Investigative Ophthalmology & Visual Science. v.6, p.2557-62, 2014. VAAJANEN, A.; VAPAATALO, H. Local Ocular Renin-Angiotensin System ? A target for Glaucoma Therapy? Basic & Clinical Pharmacology & Toxicology, v.109, p.217-224, 2011. VAAJANEN, A. Expression and function of angiotensins in the regulation of intraocular pressure. Thesis. University of Helsinki, 2009. VAAJANEN, A.; LUHTALA, S.; OKSALA, O.; VAPAATALO, H. Does the renin-angiotensin system also regulate intra-ocular pressure? Annals of Medicine, v.40, p.418?427, 2008. VICKERS, C.; HALES, P.; KAUSHIK, V.; DICK, L.; GAVIN, J.; TANG, J.; GODBOUT, K.; PARSONS, T.; BARONAS, E.; HSIEH, F.; ACTON, S.; PATANE, M.; NICHOLS, A.; TUMMINO, P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. Journal of Biology Chemistry. v.277, p.14838-14843, 2002. WAGNER, J.; JAN DANSER, A.H.; DERKX, F.H. Demonstration of rennin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular rennin-angiotensin system. British Journal of Ophthalmology, v.80, p.159?163, 1996. WANG, R.F.; PODOS, S.M.; MITTAG, T.W.; YOKOYOMA, T. Effect of CS- 088, an angiotensin AT1 receptor antagonist, on intraocular pressure in glaucomatous monkey eyes. Experimental Eye Research, v. 80, p.629-632, 2005. WATKINS, R.W.; BAUM, T.; CEDENO, K.; SMITH, E.M.; YUEN, P.H.; AHN, H.S.; BARNETT, A. Topical ocular hypotensive effects of the novel angiotensin converting enzyme inhibitor SCH 33861 in conscious rabbits. Journal of Ocular Pharmacology and Therapeutics, v.3, n.4, p.295-307, 1987. WEITZMAN, M.; CAPRIOLI, J. Medical Terapy of glaucoma. In: Tasman W, Jaeger EA (eds). Duanes?s Ophthalmology on CD-ROM. v.3, Chapter 56. Pippincot Williams et Wilkins. Philadelphia, 2006. WHITEMAN, A.L. ; KLAUSS, G.; MILLER, P.E.; DUBIELZIG, R.R. Morphologic features of degeneration and cell death in the neurosensory retina in dogs with primary angle-closure glaucoma. American Journal of Veterinary Research, v.63, p.257-261, 2002. WILKIE, D.A. Glaucoma. In: BIRCHARD, S.J.; SHERDING, R.G. Manual Saunders ? cl?nica de pequenos animais. S?o Paulo: Roca, p.1360-1366, 1998. WILLIS, A.M. Ocular hypotensive drugs. Veterinary Clinics of North America: Small Animal Practice, Philadelphia, v.34, n.3, p.755-76, 2004. WOOD, J.L.N.; LAKHANI, K.H.; MASON, I.K.; BARNETT, K.C. Relationship of the degree of goniodysgenesis and other ocular measurements to glaucoma in great danes. American Journal of Veterinary Research, v.62, p.1493?1499, 2001.

Page generated in 0.0029 seconds