Open Access Peer-reviewed

Effects of Valsartan and Telmisartan on the LungTissue Histology in Sensitized Rats

Manal A. Algaem1, Intesar T. Numan2, Saad A. Hussain2,

1Department of Pharmacology, College of Pharmacy, Al-Basra University, Iraq

2Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad, Baghdad, Iraq

American Journal of Pharmacological Sciences. 2013, 1(4), 56-60. DOI: 10.12691/ajps-1-4-3
Published online: August 25, 2017

Abstract

The renin-angiotensin system (RAS)was potentially implicated in the pathogenesis of pulmonary disorders through its involvement in inducing pro-inflammatory mediators in the lung tissues. The present study evaluates the effects of the angiotensin receptor blockers (ARBs), telmisartan and valsartan, on the histological changes of lung tissues in sensitized rats. Twenty-fourWister female rats were randomly divided into four groups: A, negative control; B, valsartan-treated group; C, telmisartan-treated group and D, positive control. The rats in the groups B-D were sensitized and challenged with ovalbumin (OVA). Group A rats were sensitized and challenged with normal saline. Rats from groups B and C were treated with either valsartan or telmisartan (5mg/kg/day), respectively. The effects of administered ARBs on lung tissue structures were histologically evaluated. Treatment with telmisartan significantly attenuates the inflammatory and the hyper-proliferative changes in lung tissue after OVA-challenge, while valsartan did not show such effect. In conclusion, telmisartan demonstrates anti-inflammatory and anti-proliferative activities in sensitized rats, while valsartan lacks these effects.

Keywords:

telmisartan, valsartan, sensitization, inflammation, lung
[1]  Hao S, Baltimore D. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat. Immunol., 10(3):281-288. 2009.View Article  PubMed
 
[2]  Wagelie-Steffen AL, Kavanaugh AF, Wasserman IS.Biologic therapies for the treatmentof asthma.Clin. Chest Med., 103:36-42. 2006.
 
[3]  Fish JE, Peters SP. Airway remodeling and persistent airway obstruction in asthma.J. Allergy Clin.Immunol., 104:509-551. 1999.View Article
 
[4]  Gosens R, Bos IS, Zaagsma J, Meurs H. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am. J. Respir. Crit. Care Med., 171:1096-1102. 2005.View Article  PubMed
 
[5]  Kakar SS, Sellers JC, Devor DC, Musgrove LC, Neill JD. Angiotensin II type-1 receptor subtype cDNAs: differential tissue expression and hormonal regulation. Biochem.Biophys. Res. Commun., 183:1090-1096. 1992.View Article
 
[6]  Kanazawa H, Kurihara N, Hirata K, Kudoh S, Fujii T, Tanaka S, et al. Angiotensin II stimulates peptide leukotriene production by guinea pig airway via the AT1 receptor pathway. Prostaglandins Leukot. Essent. Fatty Acids, 52: 241-244. 1995.View Article
 
[7]  Gosens R, Zaagsma J, Meurs H, Halayko AJ. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir. Res., 2006; 7:73. 2006.
 
[8]  Kramer C, Sunkomat J, Witte J, Luchtefeld M, Walden M, Schmidt B, et al. Angiotensin II receptor-independent anti-inflammatory and anti aggregatory properties of losartan role of the active metabolite exp3179. Circ. Res., 90:770-776. 2002.View Article  PubMed
 
[9]  Stockley RA. Progression of chronic obstructive pulmonary disease: impact of inflammation, comorbidities and therapeutic intervention.Curr. Med. Res. Opin., 25:1235-1245. 2009.View Article  PubMed
 
[10]  Marshall RP. The pulmonary renin-angiotensin system.Curr. Pharm. Des., 9:715-722. 2003.View Article  PubMed
 
[11]  Chilosi M, Poletti V, Rossi A. The pathogenesis of COPD and IPF: distinct horns of the same devil?Respir. Res., 13:3. 2012.View Article  PubMed
 
[12]  Jankowich MD, Rounds SIS. Combined pulmonary fibrosis and emphysema syndrome.Chest, 141:222-231. 2012.View Article  PubMed
 
[13]  Specks U, Martin WJ, Rohrbach MS. Bronchoalveolar lavage fluid angiotensin-converting enzyme in interstitial lung disease. Am. Rev. Respir. Dis., 141:117-123. 1990.View Article  PubMed
 
[14]  Li X, Molina-Molina M, Abdul-Hafez A, Ramirez J, Serrano-Mollar A, Xaubet A, Uhal BD. Extravascular sources of lung angiotensin peptide synthesis in idiopathic pulmonary fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol., 291:L887-L895. 2006.View Article  PubMed
 
[15]  Raupach T, Luthje L, Kogler H, Duve C, Schweda F, Hasenfuss G, Andreas S. Local and systemic effects of angiotensin receptor blockade in an emphysema mouse model. Pulm.Pharmacol.Ther., 24:215-220. 2011.View Article  PubMed
 
[16]  Xue JM, Xu YJ, Zhang ZX, et al. Effects of nitric oxide on the airway inflammation and lymphocyte proliferation in sensitized rats.Clin. J. Tuberc. Respir. Dis., 21:208-211. 1998.
 
[17]  Holsapple MP, Sehuner M, Yim GKW. Pharmacological modulation of edema mediated by prostaglandins, serotonin and histamine.Agents Action, 10:368-373. 1980.View Article  PubMed
 
[18]  Peter KG. Remodeling in asthma and chronic obstructive lung disease.Am. J. Respir. Crit. Care Med., 28:28-38. 2001.
 
[19]  Brown AJ, Nally JE. Hydrocortisone abolishes the angiotensin II-mediated potentiation of endothelin-1 in bovine bronchi. Clin. Sci. (London), 100(1):19-23. 2001.View Article
 
[20]  Nally JE, Clayton RA, Wakelam MJ, Thomson NC, McGrath JC. Angiotensin II enhances responses to endothelin-1 in bovine bronchial smooth muscle. Pulm.Pharmacol., 7(6):409-413. 1994.View Article  PubMed
 
[21]  Rao GN, Lassegue B, Alexander RW, Griendling KK. Angiotensin II stimulates phosphorylation of high-molecular-mass cytosolic phospholipase A2 in vascular smooth-muscle cells. Biochem. J.,299:197-201. 1994. PubMed
 
[22]  Gijon MA, Leslie CC. Regulation of arachidonic acid release and cytosolic phospholipase A2 activation.J. Leukoc. Biol., 65:330-336. 1999. PubMed
 
[23]  Rennard SI. Inflammation and repair processes in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 160:S12-S16. 1999.View Article  PubMed
 
[24]  Elias JA, Zhu Z, Chupp G, Homer RJ.Airway remodeling in asthma.J. Clin. Invest., 104:1001-1006. 1999.View Article  PubMed
 
[25]  Al-Hejjaj WK, Numan IT, Al-Sa'ad RZ, Hussain SA. Anti-inflammatory activity of telmisartan in rat models of experimentally-induced chronic inflammation: Comparative study with dexamethasone. Saudi Pharm. J., 19:29-34. 2011.View Article
 
[26]  Myou S, Fujimura M, Kurashima K, Tachibana H, Watanabe K, Hirose T. Type 1 angiotensin II receptor antagonism reduces antigen-induced airway reactions. Am. J. Respir. Crit. Care Med., 162: 45-49. 2000.View Article  PubMed
 
[27]  Wang T, Yin KS, Liu KY, Lu GJ, Chen JD. Effect of valsartan on the expression of angiotensin II receptors in the lung of chronic antigen exposure rats. Chin. Med. J., 121(22):2312-2319. 2008.
 
[28]  Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARγ-modulating activity. Hypertension, 43:993-1002. 2004.View Article  PubMed
 
[29]  Ushijima K, Takuma M, Ando H, Ishikawa-Kobayashi E, Nozawa M, Maekawa T, Shiga T, Fujimura A. Effects of telmisartan and valsartan on insulin sensitivity in obese diabetic mice. Eur. J. Pharmacol., 5:698(1-3):505-510. 2013.