Análise imunohistoquímica e histomorfométrica do reparo alveolar em ratos espontaneamente hipertensos (SHR) tratados com losartan

Autores

DOI:

https://doi.org/10.33448/rsd-v9i11.10634

Palavras-chave:

Losartan; Angiotensina II; Osso.

Resumo

A hipertensão é uma condição multifatorial com altos índices de complicações, como doenças cardiovasculares e renais, o que a torna um problema de saúde pública mundial. Esta doença altera a regulação do cálcio induzindo a perda óssea, que é limitada por medicamentos anti-hipertensivos. Uma dessas drogas, o losartan, inibe os receptores AT1 da angiotensina II (Ang II). O objetivo deste estudo foi comparar o processo de reparo alveolar em ratos espontaneamente hipertensos (SHR) e ratos Wistar, e avaliar o efeito do losartan na dinâmica óssea. Ratos tratados e não tratados foram submetidos à extração dentária do incisivo superior direito e eutanasiados em 7, 14 ou 28 dias após a cirurgia. O reparo alveolar foi então analisado histomorfometricamente e imunohistoquimicamente através da medição de proteínas envolvidas no metabolismo ósseo. Os dados foram analisados por meio do teste não paramétrico de Kruskal-Wallis, seguido do teste de Mann Whitney para comparação de amostras em momentos diferentes. O reparo alveolar foi lento em SHRs, enquanto o losartan aumentou a formação óssea e a espessura trabecular em SHRs e Wistars. Como as proteínas analisadas são encontradas no osso dinâmico, sugere-se que o losartan interfere nas ações da angiotensina II e do sistema renina-angiotensina e limita o metabolismo ósseo.

Referências

Afghani, A., & Goran, M. I. (2007). Lower bone mineral content in hypertensive compared with normotensive overweight Latino children and adolescents. American journal of hypertension, 20(2), 190–196. https://doi.org/10.1016/j.amjhyper.2006.07.014

Al-Majed, A. R., Assiri, E., Khalil, N. Y., & Abdel-Aziz, H. A. (2015). Losartan: Comprehensive Profile. Profiles of drug substances, excipients, and related methodology, 40, 159–194. https://doi.org/10.1016/bs.podrm.2015.02.003

Bastos, M. F., Brilhante, F. V., Gonçalves, T. E., Pires, A. G., Napimoga, M. H., Marques, M. R., & Duarte, P. M. (2010). Hypertension may affect tooth-supporting alveolar bone quality: a study in rats. Journal of periodontology, 81(7), 1075–1083. https://doi.org/10.1902/jop.2010.090705

Carvalho, A. A., de Castro, A. L., Melhado, R. M., & Bedran De Castro, J. C. (1983). Healing of tooth extraction wounds in rats with renal hypertension. A histological study. The Journal of Nihon University School of Dentistry, 25(3), 214–220. https://doi.org/10.2334/josnusd1959.25.214

Chen, S., Grover, M., Sibai, T., Black, J., Rianon, N., Rajagopal, A., Munivez, E., Bertin, T., Dawson, B., Chen, Y., Jiang, M. M., Lee, B., Yang, T., & Bae, Y. (2015). Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton. Molecular genetics and metabolism, 115(1), 53–60. https://doi.org/10.1016/j.ymgme.2015.02.006

Donmez, B. O., Ozdemir, S., Sarikanat, M., Yaras, N., Koc, P., Demir, N., Karayalcin, B., & Oguz, N. (2012). Effect of angiotensin II type 1 receptor blocker on osteoporotic rat femurs. Pharmacological reports : PR, 64(4), 878–888. https://doi.org/10.1016/s1734-1140(12)70882-4

Emanueli, C., Salis, M. B., Stacca, T., Gaspa, L., Chao, J., Chao, L., Piana, A., & Madeddu, P. (2001). Rescue of impaired angiogenesis in spontaneously hypertensive rats by intramuscular human tissue kallikrein gene transfer. Hypertension (Dallas, Tex. : 1979), 38(1), 136–141. https://doi.org/10.1161/01.hyp.38.1.136

Gealh, W. C., Pereira, C. C., Luvizuto, E. R., Garcia-Júnior, I. R., Antoniali, C., & Okamoto, R. (2014). Healing process of autogenous bone graft in spontaneously hypertensive rats treated with losartan: an immunohistochemical and histomorphometric study. Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 72(12), 2569–2581. https://doi.org/10.1016/j.joms.2014.07.010

Hatton, R., Stimpel, M., & Chambers, T. J. (1997). Angiotensin II is generated from angiotensin I by bone cells and stimulates osteoclastic bone resorption in vitro. The Journal of endocrinology, 152(1), 5–10. https://doi.org/10.1677/joe.0.1520005

Hiruma, Y., Inoue, A., Hirose, S., & Hagiwara, H. (1997). Angiotensin II stimulates the proliferation of osteoblast-rich populations of cells from rat calvariae. Biochemical and biophysical research communications, 230(1),176–178. https://doi.org/10.1006/bbrc.1996.5914

Ma, L., Ji, J. L., Ji, H., Yu, X., Ding, L. J., Liu, K., & Li, Y. Q. (2010). Telmisartan alleviates rosiglitazone-induced bone loss in ovariectomized spontaneous hypertensive rats. Bone, 47(1), 5–11. https://doi.org/10.1016/j.bone.2010.03.016

Manrique, N., Pereira, C. C., Garcia, L. M., Micaroni, S., Carvalho, A. A., Perri, S. H., Okamoto, R., Sumida, D. H., & Antoniali, C. (2012). Alveolar bone healing process in spontaneously hypertensive rats (SHR). A radiographic densitometry study. Journal of applied oral science : revista FOB, 20(2), 222–227. https://doi.org/10.1590/s1678-77572012000200017

Manrique, N., Pereira, C. C., Luvizuto, E. R., Sánchez, M., Okamoto, T., Okamoto, R., Sumida, D. H., & Antoniali, C. (2015). Hypertension modifies OPG, RANK, and RANKL expression during the dental socket bone healing process in spontaneously hypertensive rats. Clinical oral investigations, 19(6), 1319–1327. https://doi.org/10.1007/s00784-014-1369-0

Moura, A. P., Montalvany-Antonucci, C. C., Taddei, S. R., Queiroz-Junior, C. M., Biguetti, C. C., Garlet, G. P., Ferreira, A. J., Teixeira, M. M., Silva, T. A., & Andrade, I., Jr (2016). Effects of angiotensin II type I receptor blocker losartan on orthodontic tooth movement. American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics, 149(3), 358–365. https://doi.org/10.1016/j.ajodo.2015.09.019

Munzenmaier, D. H., & Greene, A. S. (2006). Chronic angiotensin II AT1 receptor blockade increases cerebral cortical microvessel density. American journal of physiology. Heart and circulatory physiology, 290(2), H512–H516. https://doi.org/10.1152/ajpheart.01136.2004

Queiroz-Junior, C. M., Silveira, K. D., de Oliveira, C. R., Moura, A. P., Madeira, M. F., Soriani, F. M., Ferreira, A. J., Fukada, S. Y., Teixeira, M. M., Souza, D. G., & da Silva, T. A. (2015). Protective effects of the angiotensin type 1 receptor antagonist losartan in infection-induced and arthritis-associated alveolar bone loss. Journal of periodontal research, 50(6), 814–823. https://doi.org/10.1111/jre.12269

Rizzoni, D., Pasini, E., Flati, V., Rodella, L. F., Paiardi, S., Assanelli, D., De Ciuceis, C., Porteri, E., Boari, G. E., Rezzani, R., Speca, S., Favero, G., Martinotti, S., Toniato, E., Platto, C., & Agabiti-Rosei, E. (2008). Angiotensin receptor blockers improve insulin signaling and prevent microvascular rarefaction in the skeletal muscle of spontaneously hypertensive rats. Journal of hypertension, 26(8), 1595–1601. https://doi.org/10.1097/HJH.0b013e328304b060

Santos, C. F., Morandini, A. C., Dionísio, T. J., Faria, F. A., Lima, M. C., Figueiredo, C. M., Colombini-Ishikiriama, B. L., Sipert, C. R., Maciel, R. P., Akashi, A. P., Souza, G. P., Garlet, G. P., Rodini, C. O., Amaral, S. L., Becari, C., Salgado, M. C., Oliveira, E. B., Matus, I., Didier, D. N., & Greene, A. S. (2015). Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue. PloS one, 10(8), e0134601. https://doi.org/10.1371/journal.pone.0134601

See S. (2001). Angiotensin II receptor blockers for the treatment of hypertension. Expert opinion on pharmacotherapy, 2(11), 1795–1804. https://doi.org/10.1517/14656566.2.11.1795

Shimizu, H., Nakagami, H., Osako, M. K., Hanayama, R., Kunugiza, Y., Kizawa, T., Tomita, T., Yoshikawa, H., Ogihara, T., & Morishita, R. (2008). Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 22(7), 2465–2475. https://doi.org/10.1096/fj.07-098954

Soltis, E. E., Jewell, A. L., Dwoskin, L. P., & Cassis, L. A. (1993). Acute and chronic effects of losartan (DuP 753) on blood pressure and vascular reactivity in normotensive rats. Clinical and experimental hypertension (New York, N.Y. : 1993), 15(1), 171–184. https://doi.org/10.3109/10641969309041618

Trippodo, N. C., & Frohlich, E. D. (1981). Similarities of genetic (spontaneous) hypertension. Man and rat. Circulation research, 48(3), 309–319. https://doi.org/10.1161/01.res.48.3.309

Tea, B. S., Dam, T. V., Moreau, P., Hamet, P., & deBlois, D. (1999). Apoptosis during regression of cardiac hypertrophy in spontaneously hypertensive rats. Temporal regulation and spatial heterogeneity. Hypertension (Dallas, Tex. : 1979), 34(2), 229–235. https://doi.org/10.1161/01.hyp.34.2.229

Whitebread, S., Mele, M., Kamber, B., & de Gasparo, M. (1989). Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochemical and biophysical research communications, 163(1), 284–291. https://doi.org/10.1016/0006-291x(89)92133-5

Yamamoto, S., Kido, R., Onishi, Y., Fukuma, S., Akizawa, T., Fukagawa, M., Kazama, J. J., Narita, I., & Fukuhara, S. (2015). Use of renin-angiotensin system inhibitors is associated with reduction of fracture risk in hemodialysis patients. PloS one, 10 (4), e0122691. https://doi.org/10.1371/journal.pone.0122691

You, D., Cochain, C., Loinard, C., Vilar, J., Mees, B., Duriez, M., Lévy, B. I., & Silvestre, J. S. (2008). Combination of the angiotensin-converting enzyme inhibitor perindopril and the diuretic indapamide activate postnatal vasculogenesis in spontaneously hypertensive rats. The Journal of pharmacology and experimental therapeutics, 325(3), 766–773. https://doi.org/10.1124/jpet.107.131532

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05/12/2020

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PEREIRA, C. C. S.; MANRIQUE, N. .; MOURA, J. de .; MULINARI-SANTOS, G. .; MONTEIRO, N. G. .; PITOL-PALIN, L. .; ANTONIALI, C. .; OKAMOTO, R. . Análise imunohistoquímica e histomorfométrica do reparo alveolar em ratos espontaneamente hipertensos (SHR) tratados com losartan. Research, Society and Development, [S. l.], v. 9, n. 11, p. e83991110634, 2020. DOI: 10.33448/rsd-v9i11.10634. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/10634. Acesso em: 22 nov. 2024.

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Ciências da Saúde