Additive Effect of TAK-491, a New Angiotensin Receptor Blocker, and Pioglitazone, in Reducing Myocardial Infarct Size

Abstract

TAK-491 and PIO independently limited myocardial IS in a dose-dependent fashion; and the effects were additive. The mechanism of protection and the role of TAK-491 in this clinical setting should be further investigated.

Aliskiren and Valsartan Reduce Myocardial AT1 Receptor Expression and Limit Myocardial Infarct Size in Diabetic Mice

“…Here, we show that both VA and AL augmented Akt phosphorylation at Ser-473 and Thr-308 after ischemia-reperfusion, and that the levels of P-Akt were highest in the AL50+Va16 group, in agreement with their smallest IS. Previously, we showed that azilsartan (TAK-491) reduced IS and increased Akt phosphorylation following ischemiareperfusion in non-diabetic rats [18]. Previous studies have also shown that ARBs increase Akt phosphorylation [27,[54][55][56] and several studies have shown that AL increases Akt phosphorylation in various experimental models [52,[57][58][59][60].…”

“…eNOS phosphorylation eNOS is involved in the delayed form of ischemic preconditioning [62] and is essential for the IS-limiting effects of statins [63]. We have shown that azilsartan (TAK-491) increases myocardial calcium-dependent NOS activity and eNOS phosphorylation at Ser-1177 following ischemia-reperfusion in the rat [18]. Losartan also increases eNOS phosphorylation in the rat heart [64].…”

“…Several studies have suggested that angiotensin converting enzyme inhibitors (ACE-I) [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and angiotensin receptor blockers (ARB) [1,2,4,[14][15][16][17][18][19][20][21][22] protect the heart against ischemia-reperfusion injury and reduce myocardial infarct size (IS) in various experimental animal models. It has been suggested that the protective effects of both ACE-Is [9-11, 13, 23] and ARBs [17,19,21] are dependent on Bradykinins.…”

Pioglitazone attenuates myocardial ischemia-reperfusion injury via up-regulation of ERK and COX-2

“…Ye et al (12) reported that 3-day pre-treatment with pioglitazone (2.5 mg/kg/d) increased ERK1/2 phosphorylation in rat heart. Another TZD, rosiglitazone, augments ERK1/2 activation in myocardium of hypercholesterolemic rabbits subjected to I/R injury (13).…”

Experimental Autoimmune Myocarditis: Role of Renin Angiotensin System

“…There were several reports indicating the myocardial apoptosis in the EAM rats and ARBs can effectively prevent it due to their action on RAS. For instance, ARB can block the endoplamic reticulum stress and caspase12 activation in the EAM rats thus prevents cardiomyocyte apoptosis (Singh et al, 2008;Tsutsui et al, 2007;Ye et al, 2010;Matsusaka et al, 2006) (Figure 1). …”