Stimualtion of angiotensin II type 2 receptors as a new approach to the therapy of pulmonary and renal fibrosis
I read today a review article by H.M. Siragy in J Clin Hypertension, 11: Suppl.1, S26-29, 2009 on angiotensin II subtype 2 receptor (AT2R): potential therapy. Apparently, stimulation of these receptors has many potential benefits including prevention of myocardial infarction, atherosclerosis, renal and pulmonary fibrosis, inflammatory injury and neurological deficits. The first synthetic small molecule agonists of this receptor were discovered by Wu et al. in the Department of Medicinal Chemistry, Uppsala University in Sweden (J Med Chem 49:7160-8, 2006). Pharmacological evaluation of their leading compound (C21) was reported by scientists from the Institute of Pharmacology at Charite, Berlin (Circulation 118:2523-32, 2008) and in abstracts of ESC/ISH meeting, Berlin, 2008. The renal antifibrotic effect of AT2R stimulation was demonstrated by Okada H et al. (Am J Nephrol 24:322-9, 2004). Sakai N et al ( J Hypertension 26:780-90, 2008) found that inhibition of AT2R signaling increased expression of type 1 collagen in isolated human fibrocytes. The publication of Siragy's article was supported by Daiichi Sankyo, Inc, a company apparently interested in promoting AT2R agonists (and possibly C21) for the treatment or prevention of cardiovascular diseases. C21 and/or a similar compound should be studied in experimental fibrosis and eventually developed as a novel antifibrotic drug.
Wednesday, December 16, 2009
Saturday, December 12, 2009
December 12, 2009
Oxygen therapy of IPF
The only IPF therapy my pulmonologist, Dr. Richard Matthay of Yale, recommends is oxygen. I am currently using it during exercise and whenever my oxygen blood saturation gets below 90%. With the delivery rate of 2L/min I can bring oxygen saturation from 85 to 95% in ca 3 to 5 minutes. When I seat queitly in my chair oxygen saturation remains above 90%, but climbing stairs to second floor immediately reduces it to 80-82%. Oxygen therapy has not been shown to prolong life, but it restores normal breathing very rapidly, it also prevents or even abolishes a cough attack. I am concerned that excess oxygen will enhance formation of reactive oxygen species (ROS), e.g. hydrogen peroxide, hydroxy radicals etc. ROS are known to enhance fibrotic process and can be expected, therefore, to shorten life expectancy.
I am treating myself with antioxidants: N-acetyl cysteine (NAC), 2 X 600 mg, vitamin C, 1 g per day and resveratrol, 60 mg per day. Hopefully, these antioxidants will prevent excessive formation of ROS.
Oxygen therapy of IPF
The only IPF therapy my pulmonologist, Dr. Richard Matthay of Yale, recommends is oxygen. I am currently using it during exercise and whenever my oxygen blood saturation gets below 90%. With the delivery rate of 2L/min I can bring oxygen saturation from 85 to 95% in ca 3 to 5 minutes. When I seat queitly in my chair oxygen saturation remains above 90%, but climbing stairs to second floor immediately reduces it to 80-82%. Oxygen therapy has not been shown to prolong life, but it restores normal breathing very rapidly, it also prevents or even abolishes a cough attack. I am concerned that excess oxygen will enhance formation of reactive oxygen species (ROS), e.g. hydrogen peroxide, hydroxy radicals etc. ROS are known to enhance fibrotic process and can be expected, therefore, to shorten life expectancy.
I am treating myself with antioxidants: N-acetyl cysteine (NAC), 2 X 600 mg, vitamin C, 1 g per day and resveratrol, 60 mg per day. Hopefully, these antioxidants will prevent excessive formation of ROS.
Subscribe to:
Posts (Atom)
