PPARgamma Activation by Losartan in Hypertensive Patients: The Importance of Losartan-Metabolites

German Heart Institute

Status

Unknown

Conditions

Hypertension

Treatments

Drug: losartan

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT00561327

P2132V1

Details and patient eligibility

About

The purpose of this study is to determine whether losartan metabolites are effective in inducing PPARγ target genes in monocytes in losartan-treated patients.

Full description

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:

Hypertensive patients chronically treated with losartan exhibit sufficient plasma levels of EXP3179 to activate PPARγ.
PPARγ target genes are induced in monocytes from losartan-treated patients.

Sex

All

Ages

19 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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).

Exclusion criteria

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.