angiotensin-i and Respiratory-Tract-Diseases

Renin-angiotensin system (RAS) plays an indispensable role in regulating blood pressure through its effects on fluid and electrolyte balance. As an aside, cumulative evidence from experimental to clinical studies supports the notion that dysregulation of RAS contributes to the pro-inflammatory, pro-oxidative, and pro-fibrotic processes that occur in pulmonary diseases like asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute lung injury (ALI). Pharmacological intervention of the various RAS components can be a novel therapeutic strategy for the treatment of these respiratory diseases. In this chapter, we first give a recent update on the RAS, and then compile, review, and analyse recent reports on targeting RAS components as treatments for respiratory diseases. Inhibition of the pro-inflammatory renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptor (AT1R) axis, and activation of the protective ACE2, AT2R, Ang (1-7), and Mas receptor axis have demonstrated varying degrees of efficacies in experimental respiratory disease models or in human trials. The newly identified alamandine/Mas-related G-protein-coupled receptor member D pathway has shown some therapeutic promise as well. However, our understanding of the RAS ligand-and-receptor interactions is still inconclusive, and the modes of action and signaling cascade mediating the newly identified RAS receptors remain to be better characterized. Clinical data are obviously lacking behind the promising pre-clinical findings of certain well-established molecules targeting at different pathways of the RAS in respiratory diseases. Translational human studies should be the focus for RAS drug development in lung diseases in the next decade.

Topics: Angiotensin I; Angiotensin II; Angiotensins; Fibrosis; Humans; Peptide Fragments; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Respiratory Tract Diseases; Signal Transduction

The authors studied the parameters of Friedland and Silverstein's technique for measuring the activity of the angiotensin I conversion enzyme and found a number of anomalies. The technique was modified by correcting the wide pH difference between the pH of the reagent and the pH of the reference solution. This modification made the technique optimal for the measurement of the enzyme activity by allowing a 20 to 40 per cent increase in this activity and a 15% increase in the positivity in cases of clinical sarcoidosis. The application of this modified test to the determination of the activity of the angiotension I conversion enzyme in control subjects, patients with sarcoidosis and patients with order respiratory diseases gave the following mean values, respectively: 39 +/- 10 IU; 81 +/- 23 IU; 41.5 +/- 2.5 IU in the serum and 0.2 IU; 1.1 +/- 0.5 IU; 0.2 +/- 0.1 IU in bronchoalveolar lavage fluid. The increase in enzyme activity in sarcoidosis is found in the serum in 75% of cases and in bronchoalveolar lavage fluid in 85% of cases. This modified technique can be applied in routine practice and in research.

Topics: Angiotensin I; Angiotensins; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Indicators and Reagents; Methods; Peptidyl-Dipeptidase A; Phosphates; Respiratory Tract Diseases; Sarcoidosis; Spectrometry, Fluorescence