Intrinsic ANG II type 1 receptor stimulation contributes to recovery of postischemic mechanical function.
To determine whether intrinsic angiotensin II (ANG II) type 1 receptor (AT1-R) stimulation modulates recovery of postischemic mechanical function, we studied the effects of selective AT1-R blockade with losartan on proton production from glucose metabolism and recovery of function in isolated working rat hearts perfused with Krebs-Henseleit buffer containing palmitate, glucose, and insulin. Aerobic perfusion (50 min) was followed by global, no-flow ischemia (30 min) and reperfusion (30 min) in the presence (n = 10) or absence (n = 14) of losartan (1 mumol/l) or the cardioprotective adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA, 0.5 mumol/l, n = 11). During reperfusion in untreated hearts (controls), left ventricular (LV) minute work partially recovered to 38% of aerobic baseline, whereas proton production increased to 155%. Compared with controls, CHA improved recovery of LV work to 79% and reduced proton production to 44%. Losartan depressed recovery of LV work to 0% without altering proton production. However, exogenous ANG II (1-100 nmol/l) in combination with losartan restored recovery of LV work during reperfusion in a concentration-dependent manner, suggesting that postischemic recovery of function depends on intrinsic AT1-R stimulation.
Ford
W R
WR
Department of Medicine, University of Alberta, Edmonton, Canada.
Clanachan
A S
AS
Lopaschuk
G D
GD
Schulz
R
R
Jugdutt
B I
BI
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D006321:Heart / Q000503:physiopathology*; D017136:Ion Transport; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*
D011522:Protons; D011945:Receptors, Angiotensin; D000804:Angiotensin II