Discrepancies between inotropic responses and beta-adrenoceptor characteristics after global ischemia in isolated hearts.
The influence of global ischemia on cardiac beta-adrenoceptors was studied in rat and guinea pig Langendorff hearts (LH), both by functional and binding experiments using the specific beta-adrenoceptor ligand (-)-[125I]-iodocyanopindolol. Neither ischemia (30 or 60 min) nor postischemic reperfusion caused any change in beta-adrenoceptor density, affinity or in the beta 1/beta 2 ratio in LH of normal rats or in LH of rats pretreated with reserpine or 6-hydroxydopamine (6-OHDA), or in guinea pig LH, whereas perfusion of rat LH with 10(-5) M isoprenaline (15 min) caused the expected decrease in beta-adrenoceptor density. After ischemia, isoprenaline was no longer able to influence beta-adrenoceptor density, suggesting that the internalization mechanism is impaired. In functional studies, perfusion of the rat LH with 10(-5) M isoprenaline (15 min) shifted the concentration-response curve for isoprenaline to the right. Thirty-minute global ischemia virtually abolished the inotropic but not the chronotropic response to isoprenaline. Ischemia did not impair the inotropic response to ouabain or to calcium, indicating that the contractile apparatus itself was still largely intact. Our results suggest that the contractile failure after ischemia is not caused by a decrease in beta-adrenoceptor density or by a defect in the contractile apparatus but by an impaired second-messenger system.
van den Ende
R
R
Division of Pharmacotherapy, Academic Medical Center, University of Amsterdam, The Netherlands.
Batink
H D
HD
Pfaffendorf
M
M
van Zwieten
P A
PA
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017298:Bisoprolol; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D017298:Bisoprolol