Dissecting out the Complex Ca2+-Mediated Phenylephrine-Induced Contractions of Mouse Aortic Segments
L-type Ca 2+ channel (VGCC) mediated Ca 2+ 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 α1adrenoreceptor stimulation and how it is modulated by small variations in resting membrane potential (V m ) of VSMC is not clear yet. Here, we show that α1-adrenoreceptor stimulation of aortic segments of C57Bl6 mice with
... henylephrine (PE) causes phasic and tonic contractions. By studying the relationship between Ca 2+ mobilisation and isometric tension, it was found that the phasic contraction was due to intracellular Ca 2+ release and the tonic contraction determined by Ca 2+ influx. The latter component involves both Ca 2+ 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 Ca 2+ influx by small variations of the VSMC V m 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 Ca 2+ release from noncontractile sarcoplasmic reticulum Ca 2+ stores. Results of this study point to a complex interactions between α1-adrenoceptor-mediated VSMC contractile performance and Ca 2+ release form contractile or non-contractile Ca 2+ stores with concomitant Ca 2+ 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. Fig 3. Effects of VGCC blockers on isometric contractions by PE. Nifedipine, verapamil and diltiazem partly inhibit isometric contractions induced by 1 μM PE in organ bath-mounted aortic segments. A) Contractions induced by 1 μM PE after incubating the segments with 1 to 100 nM nifedipine (n = 4); B) Ca 2+ channel blocker (CCB) concentration-response curves for the inhibition of contractions induced by 1 μM PE.