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Role of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in airway reactivity and inflammation in an allergic mouse model of asthma |
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| Authors: | Mehaben Patel Mangesh Kurade Sahith Rajalingam Riya Bhavsar S. Jamal Mustafa |
| Affiliation: | 1. Division of Pharmaceutical Sciences, Arnold &2. Marie Schwartz College of Pharmacy &3. Health Sciences, Long Island University, Brooklyn, NY, USA;4. Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, USA |
| Abstract: | Objective: Angiotensin II (Ang II) exerts its effects through two G-protein coupled receptors: angiotensin II type 1 receptors (AT1) and type 2 receptors (AT2). Both these receptor subtypes are poorly understood in asthma. In this study, we investigated effects of AT1 receptor antagonist losartan, novel AT2 receptor agonist novokinin and AT2 receptor antagonist PD 123319 in a mouse model of asthma. Methods: Mice were divided into control (CON) and allergen sensitized (SEN) groups. SEN was sensitized with ovalbumin (OVA) on days 1 and 6 (30?μg; i.p.), followed by 5% OVA aerosol challenge (days 11–13). Treatments included (a) losartan (SEN?+?LOS; 20?mg/kg i.p., day 14), (b) novokinin (SEN?+?NOV; 0.3?mg/kg i.p., day 14), and (c) PD 123319 (SEN?+?PD; 5?mg/kg i.p., day 14). Experiments for airway responsiveness, bronchoalveolar lavage, and tracheal ring reactivity using isolated organ bath were performed. Results: Airway responsiveness to methacholine (MCh) (48?mg/mL) was significantly higher in SEN (563.71?±?40% vs. 294.3?±?123.84 in CON). This response was potentiated in SEN?+?PD group (757?±?30%; p?p? Conclusions: These data suggest that AT1 and AT2 receptors have opposite effects in modulating airway hyperresponsiveness and inflammation in asthma. |
| Keywords: | Angiotensin II asthma angiotensin II receptors airway hyperresponsiveness inflammation |