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Abdelkrim M.A.,niversite Nantes Angers Le Mans Oniris | Mallem M.Y.,niversite Nantes Angers Le Mans Oniris | Chatagnon G.,niversite Nantes Angers Le Mans Oniris | Gogny M.,niversite Nantes Angers Le Mans Oniris | And 3 more authors.
Canadian Journal of Physiology and Pharmacology | Year: 2012

Circulating autoantibodies directed against the 2nd extracellular loop (EL-2) of β1-adrenoceptors (β1-AABs) have been detected in the serum of patients with various cardiovascular pathologies. β1-AABs induce agonistic, positive in otropic effects via β1-adrenoceptors (β1ARs). In the mammalian heart, β1-AR can exist in 2 distinct activated configurations (the so called high- and low-affinity states). The aim of the present study was to investigate whether the action of β1-AAB is dependent on the affinity state of β1AR in isolated ventricular cardio myocytes of adult Wistar rats. Immunoglobulin G (IgG) containing β1-AAB obtained from animals immunized with a peptide corresponding to the EL-2 of human β1-AR, caused a dose-dependent increase in cell shortening. Isoproterenol-induced in otropy was significantly reduced in cardio myocytes that had been preincubated with IgG containing β1-AAB and in cardio myocytes isolated from immunized rats. The negative effects of prein cubation with IgG containing β 1-AAB on the response to is oproterenol was inhibited in the presence of bisoprolol. CGP 12177A and pindolol-induced inotropy was not affected by IgG preincubation or immunization. No detectable inotropic effect of cell shortening was obtained with IgG containing β1-AAB in the presence of propranolol and 3-isobutyl- 1-methylxanthine. The present study demonstrates that β1-AABs have no agonist/antagonist-like effects upon low-affinity state β1-ARs. This result indicates that β1-AABs recognize and stabilize the high-affinity state, but are unable to stabilize and (or) induce the low-affinity state receptor. Source

Abdelkrim M.A.,niversite Nantes Angers Le Mans Oniris | Martignat L.,niversite Nantes Angers Le Mans Oniris | Gogny M.,niversite Nantes Angers Le Mans Oniris | Desfontis J.-C.,niversite Nantes Angers Le Mans Oniris | And 3 more authors.
Canadian Journal of Physiology and Pharmacology | Year: 2013

In porcine coronary arteries (PCAs), celiprolol, a selective β1-adrenoceptors antagonist, induces vasodilatation by an endothelium- and nitric oxide (NO)-dependent pathway. However, the mechanisms of that vascular effect have not been precisely established. β3-Adrenoceptors have been shown to be involved in the relaxation per se of various vascular beds, including coronary vessels. Thus, we evaluated (i) the presence of β3-adrenoceptors in the PCA and (ii) their role in celiprolol induced vasodilatation. PCA rings were placed in organ baths and preconstricted with KCl. All experiments were performed in the presence of nadolol (a β1/β2-adrenoceptor antagonist). Cumulative concentration-response curves to SR 58611A and ICI 215001 (2 β3-adrenoceptor agonists) and to celiprolol were constructed. We also used semiquantitative reverse transcription -polymerase chain reaction, which clearly showed the presence of β3-adrenoceptor transcripts. SR 58611A, ICI 215001, and celiprolol induced concentration-dependent relaxations in PCA rings. SR 58611A-induced relaxation was almost abolished after removal of endothelium or pretreatment with L-NAME (a NO synthase inhibitor). The vasorelaxations induced by SR 58611A and celiprolol were inhibited in the presence of SR 59230A and L-748337 (2 selective β3-adrenoceptor antagonists). We showed (i) that PCAs possess functional β3-adrenoceptors mediating endothelium- and NO-dependent relaxation, and (ii) that celiprolol exerts a β3-adrenoceptor agonistic activity in this vascular bed. Source

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