Dissecting out the Complex Ca(2+)-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 α1-adrenoreceptor 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 phenylephrine (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 non-contractile 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.