Análisis inmunohistoquímico e histomorfométrico de la reparación alveolar en ratas espontáneamente hipertensas (SHR) tratadas con losartan

Autores/as

DOI:

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

Palabras clave:

Losartán; Angiotensina II; Hueso.

Resumen

La hipertensión es una enfermedad multifactorial con altas tasas de complicaciones, como enfermedades cardiovasculares y renales, lo que la convierte en un problema de salud pública mundial. Esta enfermedad altera la regulación del calcio induciendo la pérdida ósea, que está limitada por fármacos antihipertensivos. Uno de estos fármacos, losartán, inhibe lo receptores AT1 de angiotensina II (Ang II). El objetivo de este estudio fue comparar el proceso de reparación alveolar en ratas espontáneamente hipertensas (SHR) y ratas Wistar, y evaluar el efecto del losartán sobre la dinámica ósea. Las ratas tratadas y no tratadas se sometieron a extracción dental del incisivo superior derecho y se sacrificaron 7, 14 o 28 días después de la cirugía. La reparación alveolar se analizó luego histomorfométricamente e inmunohistoquímicamente midiendo las proteínas implicadas en el metabolismo óseo. Los datos se analizaron mediante la prueba no paramétrica de Kruskal-Wallis, seguida de la prueba de Mann Whitney para comparar muestras en diferentes momentos. La reparación alveolar fue lenta en SHR, mientras que losartán aumentó la formación ósea y el grosor trabecular en SHR y Wistars. Como las proteínas analizadas se encuentran en hueso dinámico, se sugiere que losartán interfiere con las acciones de la angiotensina II y el sistema renina-angiotensina y limita el metabolismo óseo.

Citas

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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Publicado

05/12/2020

Cómo citar

PEREIRA, C. C. S.; MANRIQUE, N. .; MOURA, J. de .; MULINARI-SANTOS, G. .; MONTEIRO, N. G. .; PITOL-PALIN, L. .; ANTONIALI, C. .; OKAMOTO, R. . Análisis inmunohistoquímico e histomorfométrico de la reparación alveolar en ratas espontáneamente hipertensas (SHR) tratadas con 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: 17 jul. 2024.

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Sección

Ciencias de la salud