Figure 8. Proposed cold-induced vasoconstriction signalling pathway in young and aged mice.
The local cold exposure produces rapid vasoconstriction which is significantly blunted in the aged mice (see blood flow graph at top centre). Cold water (4 °C) exposure to hindpaw activates the cold receptors TRPA1 and TRPM8 in sympathetic nerves, which leads to increased intracellular calcium and release of NA. This signalling, however, is significantly downregulated in aged mice due to diminished expression of TRPA1/TRPM8 in sympathetic nerves. NA acts on the post-synaptic α2c adrenergic receptors on smooth muscle cells to mediate vasoconstriction. However, α2c adrenergic receptor are also significantly diminished in aged mice, which leads to reduced signalling. All these factors contribute to an attenuated vascular cold response in aged mice compared to young mice.