Effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors on the hamster tracheal mucosal barriers to pseudomonas aeruginosa infection.

Loading...
Thumbnail Image
Date
2023
Authors
Mubbunu, Lumamba
Journal Title
Journal ISSN
Volume Title
Publisher
The University of Zambia
Abstract
The severe cases of COVID-19 observed in patients with hypertension and diabetes have created controversies as to why this was the case and the role of ARBs, and ACE inhibitors was not ruled out as a contributing factor since the induction of cough is one of their major side effects. Studies have found that the expression level of ACE2 in cells was significantly reduced after COVID-19 infection, leading to an increased level of angiotensin II and activation of the reninangiotensin-aldosterone system, thus over-activating the angiotensin II type 1 receptor of lung cells to induce and aggravate lung injury. ARBs and ACEIs interfere with the renin-angiotensin aldosterone system in producing their therapeutic effect. The function of gas exchange for the respiratory system exposes it to foreign particles, including infectious agents, allergens, and other substances that can damage it. The role of the airway mucosa is to act as a physical barrier between the external environment and the internal environment. The mucosal barrier function is composed of the mucociliary escalator, intercellular apical junction complexes that regulate paracellular permeability, and antimicrobial peptides secreted by airway epithelial cells. The three components work together to protect the respiratory tract, and impairment of one or more of these components may increase the susceptibility of the respiratory system to infections. Respiratory mucins are very important for the viscoelasticity properties of respiratory mucus, and an increase in the secretion of respiratory mucins can negatively affect the mucociliary escalator. This study aimed to investigate the effects of ACE inhibitors and ARBs on inflammatory mediators and how inflammatory mediators affect tracheal mucosal barriers. The study used a hamster (Mesocricetus auratus) as an experimental animal model and ELISA techniques to assess the increase or decrease in Bradykinin, MUC5AC, MUC5B, and FOXA2. Additionally, histological techniques were used to assess goblet cell hyperplasia and hyperplasia of the submucosal glands of the tracheal mucosa. Furthermore, the study challenged hamsters treated with enalapril or losartan with 0.2 ml of pH 7.0 containing 1.5 x 108 cfu / ml of Pseudomonas aeruginosa to assess the effects of ARB and ACEI on tracheal mucosa barriers. Dunnett’s t-test was used to analyze the results and a p-value less than 0.05 was considered significant. Hamsters treated with enalapril, or losartan had an increase in bradykinin, MUC5AC and MUC5B concentration compared to the control, however, the increase was not significant (p > 0.05). On the contrary, hamsters treated with enalapril, or Losartan had a decrease in FOXA2 concentration, however, the decrease was also not significant (p > 0.05). In histological sections, hyperplasia of goblet cells and submucosal glands was not observed. For Pseudomonas aeruginosa challenge, no hamster developed fever after 72 hours and there was no mortality at the end of 14 days. The results of this study show that the administration of enalapril or losartan did not have a significant effect on the expression of FOXA2, MUC5AC and MUC5B. Furthermore, the administration of enalapril or losartan did not cause the hamsters to develop hyperplasia of the goblet cells or submucosal glands. Finally, the administration of enalapril or Losartan did not cause the hamsters to develop fever. The implication is that enalapril and Losartan did not have a negative effect on the tracheal mucosal barrier function to Pseudomonas aeruginosa infection at a dose of 3.0 x 107 cfu/ml. In general, the findings of this study show that administration of enalapril or losartan does not significantly increase the production of respiratory tract mucins. Therefore, the administration of these drugs will not reduce the innate immune response of the respiratory tract through the impairment of mucus production and thus will not increase the susceptibility of individuals to Pseudomonas aeruginosa infection.
Description
Thesis of Doctor of Philosophy in Infectious Diseases.
Keywords
Citation