Enhancement of beta-adrenoceptor function after reperfusion following cardioplegic arrest in rat hearts.
We investigated alterations in a beta-adrenoceptor (BAR) system after reperfusion following hypothermic ischemia induced by a high-potassium (18 meq/liter) cardioplegic solution in isolated rat hearts. Materials were divided into two groups: the reperfusion group (Gr-R, n = 5) with 40 min reperfusion following 40 min cardioplegic arrest (10 degrees C) and the control group (Gr-C, n = 5) with no ischemia as time-matched perfused control. BAR and adenylate cyclase activities in crude membrane fractions were compared. Results showed that basal, NaF-, and forskolin-stimulated adenylate cyclase activity did not differ between the two groups. The maximal enzyme activity in the presence of 10(-4) M (-)-isoproterenol was higher in Gr-R than in Gr-C, while the net activity stimulated by (-)-isoproterenol was 74% higher in Gr-R than in Gr-C. The [125I]Iodocyanopindolol [( 125I]CYP) binding assay showed that BAR density was 14% higher in Gr-R than in Gr-C, while the affinity was not significantly different. The IC50 values of (-)-isoproterenol for [125I]CYP binding were lower in Gr-R than in Gr-C and the proportion of high-affinity binding sites was higher in Gr-R than in Gr-C. These data showed that 40 min reperfusion following hypothermic cardioplegic arrest (40 min) resulted in significant increases in myocardial BAR density and maximal (-)-isoproterenol-stimulated adenylate cyclase activity, and enhancement of BAR affinity for beta-adrenergic agonists due to the increase in the proportion of high-affinity binding sites.
1st Department of Surgery, Osaka University School of Medicine, Japan.
N
N
Sakagoshi
Y
Y
Watanabe
H
H
Matsuda
Y
Y
Kawashima
H
H
Yoshida
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006324:Heart Arrest, Induced; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015425:Myocardial Reperfusion; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol