Imaging sympathetic neurogenic Ca2+ signaling in blood vessels.

We review the information that has been provided by optical imaging experiments directed at understanding the role and effects of sympathetic nerve activity (SNA) in the functioning of blood vessels. Earlier studies utilized electric field stimulation of nerve terminals (EFS) in isolated arteries and vascular tissues (ex vivo) to elicit SNA, but more recently, imaging studies have been conducted in vivo, enabling the study of SNA in truly physiological conditions. Ex vivo: In vascular smooth muscle cells (VSMC) of isolated arteries, the three sympathetic neurotransmitters, norepinephrine (NE), ATP and neuropeptide Y (NPY), elicit or modulate distinct patterns of Ca2+ signaling, as revealed by confocal imaging of exogenous fluorescent Ca2+ indicators. Purinergic junctional Ca2+ transients (jCaTs) arise from Ca2+ influx during excitatory junction potentials (eJPs), and are associated with the initial neurogenic contraction. Adrenergic Ca2+ waves and oscillations cause contraction while SNA-induced endothelial Ca2+ 'pulsars' cause relaxation. In vivo: optical biosensor mice, which express genetically encoded Ca2+ indicators (GECI's) specifically in smooth muscle, combined with non-invasive imaging techniques has enabled imaging SNA-induced Ca2+ signaling and arterial diameter in vivo. SNA induces Ca2+ oscillations in intact arteries. [Ca2+] of arterial smooth muscle cells increased in hypertension, in association with increased SNA. High resolution imaging has revealed local sympathetic, neurogenic Ca2+ signaling within smooth muscle and endothelial cells of the vasculature. The ongoing development of in vivo imaging together with an expanding availability of different biosensor animals promises to enable the further assessment of SNA and its effects in the vasculature of living animals.