Contrasting inotropic responses to α1-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 α1-adrenergic receptor (α1-AR) stimulation. We compared α1-AR inotropy of cardiac trabeculae from the LV versus RV of adult mouse hearts. As previously reported, for mouse RV trabeculae, α1-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 (α1A-AR) with A-61603 also mediated contrasting LV/RV inotropy, suggesting differential activation of multiple α1-AR-subtypes was not involved. Contrasting LV/RV α1-AR inotropy was not abolished by inhibiting protein kinase C, suggesting differential activation of PKC isoforms was not involved. However, contrasting LV/RV α1-AR inotropic responses did involve different effects on myofilament Ca2+ sensitivity: submaximal force of skinned trabeculae was increased by PE pretreatment for LV but was decreased by PE for RV. For LV myocardium, α1-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 α1-AR stimulation, involving different effects on myofilament function and myosin light chain phosphorylation.