title: Modulation of myocardial stiffness by β-adrenergic stimulation--its role in normal and failing heart.
abstract: The acute effects of beta-adrenergic stimulation on myocardial stiffness were evaluated. New-Zealand white rabbits were treated with saline (control group) or doxorubicin to induce heart failure (HF) (DOXO-HF group). Effects of isoprenaline (10(-10)-10(-5) M), a non-selective beta-adrenergic agonist, were tested in papillary muscles from both groups. In the control group, the effects of isoprenaline were also evaluated in the presence of a damaged endocardial endothelium, atenolol (beta(1)-adrenoceptor antagonist), ICI-118551 (beta(2)-adrenoceptor antagonist), KT-5720 (PKA inhibitor), L-NNA (NO-synthase inhibitor), or indomethacin (cyclooxygenase inhibitor). Passive length-tension relations were constructed before and after adding isoprenaline (10(-5) M). In the control group, isoprenaline increased resting muscle length up to 1.017+/-0.006 L/L(max). Correction of resting muscle length to its initial value resulted in a 28.5+/-3.1 % decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the isoprenaline-induced right-downward shift of the passive length-tension relation. These effects were modulated by beta(1)- and beta(2)-adrenoceptors and PKA. In DOXO-HF group, the effect on myocardial stiffness was significantly decreased. We conclude that beta-adrenergic stimulation is a relevant mechanism of acute neurohumoral modulation of the diastolic function. Furthermore, this study clarifies the mechanisms by which myocardial stiffness is decreased.
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: I
authors.initials: I
authors.lastname: Falcao-Pires
authors.forename: A P
authors.initials: AP
authors.lastname: Fontes-Sousa
authors.forename: L
authors.initials: L
authors.lastname: Lopes-Conceiçao
authors.forename: C
authors.initials: C
authors.lastname: Brás-Silva
authors.forename: A F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits
chemical_list: D000318:Adrenergic beta-Agonists; D007545:Isoproterenol