The losartan metabolite EXP3179 potently induces the activity of the peroxisome proliferator-activated receptor γ (PPAR-γ) as a partial agonist in vitro. PPAR-γ is a nuclear hormone receptor and functions as a regulator of lipid- and glucose metabolism. PPAR-γ ligands improve insulin sensitivity and glucose tolerance, and reduce cardiovascular morbidity and mortality in diabetic patients.
Angiotensin II receptor 1-blocking and PPAR-γ-activating properties of losartan metabolites in patients would markedly improve the pharmacological profile of losartan by combining anti-hypertensive and highly beneficial metabolic actions. We developed the following hypothesis:
1. Hypertensive patients chronically treated with losartan exhibit sufficient plasma levels of EXP3179 to activate PPARγ.
2. PPARγ target genes are induced in monocytes from losartan-treated patients.
Age
19–80
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
Age: 19-80
Sex: male or female
Prior diagnosis of treated hypertension
Treatment with losartan 100mg/daily during at least the past 2 months (n=20/ case);
or: no prior angiotensin receptor 1-blocker treatment during the last 2 months (n=10/ control).
You may not be if
Non-steroidal anti-inflammatory drugs (exception: Acetyl salicylic acid) for the past 21 days (due to structural homologies to glitazones, and activating effects on PPARγ)
Therapy with glitazones for the past 21 days.
Clareo Health | PPARgamma Activation by Losartan in Hypertensive Patients: The Importance of Losartan-Metabolites
