Regulation of beta-adrenoceptors in a rat model of cardiac failure: effect of perindopril.
This study investigated the effects of myocardial infarction (MI)-induced cardiac failure and treatment with an angiotensin-converting enzyme (ACE) inhibitor perindopril (2 mg/kg/day) on rat beta-adrenoceptor (beta-ar) subtypes in anatomically defined regions of infarcted left ventricular (LV) free wall and noninfarcted tissue from right ventricle (RV) by using autoradiography. After 5 weeks of MI, rats with large MI size (>42%) had developed cardiac failure and beta1-ars were significantly decreased (-59%; p < 0.01) in the border region of the infarcted LV and almost abolished in the infarcted area (-90%; p < 0.005) compared with normal LV from sham-operated controls. The beta-ar changes were not found in the noninfarcted area of the same LV or in RV. MI did not significantly alter the number of beta2-ar subtypes in any region of the ventricles. Perindopril treatment for 4 weeks reduced mean cardiac region weights but did not affect beta-ar density in any cardiac region in either sham-operated or MI rats. These results indicate that cardiac failure due to MI causes significant downregulation of beta1-ars only in border and infarcted regions of rat LV and no change in beta2-ar in any area. It also suggests that the improved response of the infarcted rat heart to isoprenaline stimulation after ACE inhibitors does not result from changes in the numbers of cardiac beta-ars.
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
X H
XH
Gu
A R
AR
Kompa
R J
RJ
Summers
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D020120:Iodocyanopindolol; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D020913:Perindopril; D010869:Pindolol / Q000031:analogs & derivatives; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D011506:Proteins; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D020913:Perindopril