Effect of beta-adrenergic blockade on nucleoside release from the hypoperfused isolated heart.
Myocardial ischemia increases the release of adenosine (RADO), inosine (RINO), and norepinephrine; however, it is not known whether norepinephrine contributes to nucleoside production via the beta-adrenergic receptor. We used a Langendorff preparation (guinea pig) to study the time course of RADO and RINO during myocardial hypoperfusion (MH) produced by decreasing perfusion pressure from 60 to 30 cmH2O. Data are expressed as means +/- SE. RADO and RINO significantly increased from 21 +/- 2 and 418 +/- 89 pmol X min-1 X g-1 to 206 +/- 26 and 2,401 +/- 598, respectively, by 10 min of MH. By 20 min, RADO and RINO had decreased significantly to 111 +/- 15 and 912 +/- 169 pmol X min-1 X g-1. RADO remained at that level for the remaining 160 min, whereas RINO returned to the control level. Coronary flow and myocardial O2 consumption were constant during MH. In the presence of 10(-7) M dl-propranolol MH did not produce the initial peak RADO; RADO increased to 95 +/- 18 pmol X min-1 X g-1 at 10 min and then did not change. Also, the initial peak RINO was significantly reduced (687 +/- 67 pmol X min-1 X g-1 at 10 min). Similar results were obtained with atenolol (5 X 10(-6) M), a beta-receptor antagonist without membrane-stabilizing effects. In the presence of 10(-5) M dl-propranolol, MH did not increase nucleoside release above control. Nucleoside release was similarly blocked during MH in the presence of 5 X 10(-6) M d-propranolol, which does not have the beta-blocking properties of the l-isomer.(ABSTRACT TRUNCATED AT 250 WORDS)
D000241:Adenosine / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D003326:Coronary Circulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007288:Inosine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism*; D010101:Oxygen Consumption; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D012039:Regional Blood Flow; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D009705:Nucleosides; D001262:Atenolol; D007288:Inosine; D011433:Propranolol; D000241:Adenosine; D009638:Norepinephrine