Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.
We ligated the left anterior descending coronary artery for 1 or 2 h in 31 purebred beagles. We did not detect any changes in beta-adrenergic receptor density or affinity when normal and ischemic zones were compared, either in the subendocardium or in the subepicardium. In the ischemic zones, there was a significant decline in all measures of adenylate cyclase activity, including activity mediated by the beta-adrenergic receptor. By contrast, after chronic beta-adrenergic blockade (1.5 mg/kg propranolol i.v. twice daily for 7 d), there was an increase in adenylate cyclase activity stimulated by (-)-isoproterenol relative to adenylate cyclase activity stimulated by guanyl-5'imidodiphosphate (GppNHp) in both normal and ischemic tissue, suggesting that one effect of chronic beta blockade may be to enhance coupling between the stimulatory guanine nucleotide regulatory protein (Gs) and the beta-adrenergic receptor, despite a reduction in the number or function of Gs units. Chronic beta blockade also led to up regulation of beta-adrenergic receptor density in subepicardial regions. After 20 min of reperfusion following 2 h of ischemia, adenylate cyclase activity tended to return to control levels, particularly in the subepicardium, where (-)-isoproterenol-stimulated adenylate cyclase activity was not different from normal myocardium. We conclude that chronic beta-adrenergic blockade may have beneficial effects during prolonged episodes of myocardial ischemia by preserving signal transduction mediated by the beta-adrenergic receptor.
Karliner
J S
JS
Cardiology Section, Veterans Administration Medical Center, San Francisco, California 94121.
Stevens
M B
MB
Honbo
N
N
Hoffman
J I
JI
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D019204:GTP-Binding Proteins / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D012969:Sodium Fluoride; D011433:Propranolol; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol