(Circulation. 1997;96:922-926.)
© 1997 American Heart Association, Inc.
Articles |
Increase in Angiotensin II Type 1 Receptor Expression Immediately After Ischemia-Reperfusion in Isolated Rat Hearts
From the Departments of Medicine, Pediatrics, and Physiology, University of Florida and VA Medical Center, Gainesville.
Correspondence to J.L. Mehta, MD, PhD, Department of Medicine, University of Florida College of Medicine, 1600 Archer Rd, PO Box 100277 JHMHC, Gainesville, FL 32610. E-mail mehta.medcs0{at}shands.ufl.edu
Background Myocardial ischemia is known to upregulate the systemic renin-angiotensin system, which influences myocardial ischemic events by affecting hemodynamics and hemostatic activity. This study was designed to examine whether angiotensin II (Ang II) receptor expression in the myocardium is altered immediately after ischemia-reperfusion.
Methods and Results Isolated buffer-perfused Sprague-Dawley rat hearts were subjected to continuous perfusion (control, n=5) or to 25 minutes of global ischemia followed by 30 minutes of reperfusion (n=10). Autoradiographic analysis for Ang II receptors of multiple myocardial sections was performed. Whereas continuous perfusion of hearts resulted in minor changes in coronary perfusion pressure (CPP), left ventricular end-diastolic pressure (LVEDP), and developed left ventricular pressure (dLVP=LVSP-LVEDP), ischemia-reperfusion caused a marked increase in CPP and LVEDP and a decrease in dLVP, indicating severe cardiac dysfunction. Concurrently, total myocardial Ang II receptor expression was greater (P<.05) in hearts subjected to ischemia-reperfusion than in the continuously perfused control hearts. Most of the increase in Ang II receptor expression was due to an increase in type 1 receptor (AT1) expression (34.6±6.5 versus 18.2±4.4 fmol/g, P<.05), because Ang II type 2 receptor expression was unaffected. To examine the importance of AT1 receptor expression, another group of isolated rat hearts (n=5) was perfused with buffer containing losartan (10-5 mol/L) and subjected to ischemia followed by reperfusion. Perfusion of hearts with losartan attenuated the ischemia-reperfusion–induced cardiac dysfunction. Perfusion of hearts with losartan also blocked the ischemia-reperfusion–induced increase in myocardial AT1 binding.
Conclusions These observations indicate that myocardial AT1 expression increases immediately after ischemia-reperfusion and contributes to cardiac dysfunction.
Key Words: angiotensin • ischemia • reperfusion • myocardium
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