Effect of chronic AT(1) receptor antagonism on postischemic functional recovery and AT(1)/AT(2) receptor proteins in isolated working rat hearts.
To determine whether chronic angiotensin II (Ang II) type I receptor (AT(1)R) antagonism improves recovery of left ventricular (LV) function after ischemia-reperfusion (IR) and increases AT(1)R and Ang II type 2 receptor (AT(2)R) protein expression in isolated working rat hearts, rats were randomized to pretreatment with either losartan (30 mg/kg/day) or UP269-6 (3 mg/kg/day), or no drug (control), for 1 week or 3 weeks before IR (50 min perfusion, 25 min ischemia, 40 min reperfusion). In vitro LV work and power and ex vivo AT(1)R and AT(2)R proteins (immunoblots) were measured. Compared to baseline perfusion, LV work and power showed variable recovery in control, losartan, and UP269-6 groups. Compared to control, losartan preserved recovery of LV work and power while UP269-6 showed less recovery after IR at both 1 week and 3 weeks. Both antagonists increased AT(2)R but not AT(1)R protein. The duration of pretreatment did not affect the expression of AT(1)R or AT(2)R proteins. The results indicate that chronic AT(1)R blockade over 1 or 3 weeks increases AT(2)R (not AT(1)R) protein expression and may preserve but not improve postischemic functional recovery compared to controls in isolated working rat hearts.
Moudgil
R
R
Division of Cardiology, Department of Medicine, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Xu
Y
Y
Menon
V
V
Jugdutt
B I
BI
D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D011743:Pyrimidines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; C088791:UP 269-6; D019808:Losartan