KCa channels are major contributors to ATP-induced cutaneous vasodilation in healthy older adults

Abstract

Objective: To examine the contributions of calcium-activated K⁺ (K_Ca) channels and nitric oxide synthase (NOS) to adenosine triphosphate (ATP)-induced cutaneous vasodilation in healthy older adults.

Methods: In eleven older adults (69 ± 2 years, 5 females), cutaneous vascular conductance, normalized to maximum vasodilation (%CVC_max) was assessed at four dorsal forearm skin sites that were continuously perfused with either 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (TEA, K_Ca channel blocker), 3) 10 mM N^ω-nitro-L-arginine (L-NNA, NOS inhibitor), or 4) combined 50 mM TEA +10 mM L-NNA, via microdialysis. Local skin temperature was fixed at 33 °C at all sites with local heaters throughout the protocol while the cutaneous vasodilator response was assessed during coadministration of ATP (0.03, 0.3, 3, 30, 300 mM; 20 min per dose), followed by 50 mM sodium nitroprusside and local skin heating to 43 °C to achieve maximum vasodilation (20-30 min).

Results: Blockade of K_Ca channels blunted %CVC_max relative to Control from 0.3 to 300 mM ATP (All P < 0.05). A similar response was observed for the combined K_Ca channel blockade and NOS inhibition site from 3 to 300 mM ATP (All P < 0.05). Conversely, NOS inhibition alone did not influence %CVC_max across all ATP doses (All P > 0.05).

Conclusion: In healthy older adults, K_Ca channels play an important role in modulating ATP-induced cutaneous vasodilation, while the NOS contribution to this response is negligible.

Keywords: Heat loss; Microdialysis; Purinergic; Skin blood flow; Thermoregulation.