Ragaglitazar is a novel and potent dual
peroxisome proliferators activated receptor (
PPAR) alpha and gamma activator. The aim of this study is to investigate the effect of
ragaglitazar on blood pressure and endothelial function in
insulin resistant animal model and non-
insulin resistant hypertensive models. The effects
ragaglitazar were tested in Zucker fa/fa, spontaneously hypertensive rats (SHR), 2 kidney 1clip rat (2K1C) and Wistar Kyoto rats (WKY).
Pioglitazone was taken as a comparative standard.
Ragaglitazar showed significant reduction (P<0.001) of systolic blood pressure (SBP) in
insulin resistant fa/fa rats, with concomitant reduction in plasma
triglycerides (TG) and
insulin levels while
pioglitazone (10 mg kg(-1)) showed significant (P<0.05) but comparatively less reduction.
Ragaglitazar in contrast to
pioglitazone showed significant reduction (P<0.05) of SBP in SHR, 2K1C while the same dose did not have any effect on normotensive WKY.
Ragaglitazar also showed significant improvement in
acetylcholine-induced relaxation in isolated aorta of Zucker fa/fa, SHR, 2K1C and also potentiated the
insulin-induced vasorelaxation in Zucker fa/fa rats. These findings summarize that
ragaglitazar shows significant reduction of BP and improvement in endothelial function not only in
insulin resistant but also in non-
insulin resistant hypertensive models where standard
thiazolidinediones are ineffective. These data indicates that dual
PPARalpha and gamma activator
ragaglitazar can be beneficial for the treatment of
hypertension and
vascular disease commonly associated with
type 2 diabetes.