title: Contrasting inotropic responses to alpha1-adrenergic receptor stimulation in left versus right ventricular myocardium.
abstract: The left ventricle (LV) and right ventricle (RV) have differing hemodynamics and embryological origins, but it is unclear whether they are regulated differently. In particular, no previous studies have directly compared the LV versus RV myocardial inotropic responses to alpha(1)-adrenergic receptor (alpha(1)-AR) stimulation. We compared alpha(1)-AR inotropy of cardiac trabeculae from the LV versus RV of adult mouse hearts. As previously reported, for mouse RV trabeculae, alpha(1)-AR stimulation with phenylephrine (PE) caused a triphasic contractile response with overall negative inotropy. In marked contrast, LV trabeculae had an overall positive inotropic response to PE. Stimulation of a single subtype (alpha(1A)-AR) with A-61603 also mediated contrasting LV/RV inotropy, suggesting differential activation of multiple alpha(1)-AR-subtypes was not involved. Contrasting LV/RV alpha(1)-AR inotropy was not abolished by inhibiting protein kinase C, suggesting differential activation of PKC isoforms was not involved. However, contrasting LV/RV alpha(1)-AR inotropic responses did involve different effects on myofilament Ca(2+) sensitivity: submaximal force of skinned trabeculae was increased by PE pretreatment for LV but was decreased by PE for RV. For LV myocardium, alpha(1)-AR-induced net positive inotropy was abolished by the myosin light chain kinase inhibitor ML-9. This study suggests that LV and RV myocardium have fundamentally different inotropic responses to alpha(1)-AR stimulation, involving different effects on myofilament function and myosin light chain phosphorylation.
authors.affiliation: VA Medical Center, Cardiology Division (111C 4150 Clement St., San Francisco, CA 94121, USA.
authors.forename: Guan-Ying
authors.initials: GY
authors.lastname: Wang
authors.forename: Diana T
authors.initials: DT
authors.lastname: McCloskey
authors.forename: Sally
authors.initials: S
authors.lastname: Turcato
authors.forename: Philip M
authors.initials: PM
authors.lastname: Swigart
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Baker
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000502:physiology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D016276:Ventricular Function
chemical_list: C094643:A 61603; D000316:Adrenergic alpha-Agonists; D001381:Azepines; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007527:Isoenzymes; D018340:Receptors, Adrenergic, alpha-1; D013764:Tetrahydronaphthalenes; C056218:ML 9; D010656:Phenylephrine; D011493:Protein Kinase C