title: Dissecting out the complex Ca2+-mediated phenylephrine-induced contractions of mouse aortic segments.
abstract: L-type Ca2+ channel (VGCC) mediated Ca2+ influx in vascular smooth muscle cells (VSMC) contributes to the functional properties of large arteries in arterial stiffening and central blood pressure regulation. How this influx relates to steady-state contractions elicited by α1-adrenoreceptor stimulation and how it is modulated by small variations in resting membrane potential (Vm) of VSMC is not clear yet. Here, we show that α1-adrenoreceptor stimulation of aortic segments of C57Bl6 mice with phenylephrine (PE) causes phasic and tonic contractions. By studying the relationship between Ca2+ mobilisation and isometric tension, it was found that the phasic contraction was due to intracellular Ca2+ release and the tonic contraction determined by Ca2+ influx. The latter component involves both Ca2+ influx via VGCC and via non-selective cation channels (NSCC). Influx via VGCC occurs only within the window voltage range of the channel. Modulation of this window Ca2+ influx by small variations of the VSMC Vm causes substantial effects on the contractile performance of aortic segments. The relative contribution of VGCC and NSCC to the contraction by α1-adrenoceptor stimulation could be manipulated by increasing intracellular Ca2+ release from non-contractile sarcoplasmic reticulum Ca2+ stores. Results of this study point to a complex interactions between α1-adrenoceptor-mediated VSMC contractile performance and Ca2+ release form contractile or non-contractile Ca2+ stores with concomitant Ca2+ influx. Given the importance of VGCC and their blockers in arterial stiffening and hypertension, they further point toward an additional role of NSCC (and NSCC blockers) herein.
authors: Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors: Paul
authors: P
authors: Fransen
authors: Department of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors: Cor E
authors: CE
authors: Van Hove
authors: Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors: Arthur J A
authors: AJ
authors: Leloup
authors: Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors: Wim
authors: W
authors: Martinet
authors: Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors: Guido R Y
authors: GR
authors: De Meyer
authors: Department of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors: Katrien
authors: K
authors: Lemmens
authors: Department of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
authors: Hidde
authors: H
authors: Bult
authors: Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors: Dorien M
authors: DM
authors: Schrijvers
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology; D009213:Myography / Q000379:methods; D010656:Phenylephrine / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D002118:Calcium