Nitric oxide (NO) increases cutaneous blood flow; however, the underpinning mechanism(s) remains to be elucidated. We hypothesized that the cutaneous blood flow response during intradermal administration of sodium nitroprusside (SNP, a NO donor) is regulated by calcium-activated potassium (KCa) channels and cyclooxygenase (COX) in young adults. We also hypothesized that these contributions are diminished in older adults given that aging can downregulate KCa channels and reduce COX-derived vasodilator prostanoids. In 10 young (23±5 years) and 10 older (54±4 years) adults, cutaneous vascular conductance (CVC) was measured at four forearm skin sites infused with 1) Ringer's (Control), 2) 50mM tetraethylammonium (TEA), a non-specific KCa channel blocker, 3) 10mM ketorolac, a non-specific COX inhibitor, or 4) 50mM TEA+10mM ketorolac via intradermal microdialysis. All skin sites were co-infused with incremental doses of SNP (0.005, 0.05, 0.5, 5, 50mM each for 25min). During SNP administration, CVC was similar at the ketorolac site (0.005-50mM, all P>0.05) relative to Control, but lower at the TEA and TEA+ketorolac sites (0.005-0.05mM, all P<0.05) in young adults. In older adults, ketorolac increased CVC relative to Control during 0.005-0.05mM SNP administration (all P<0.05), but this increase was not observed when TEA was co-administered (all P>0.05). Furthermore, TEA alone did not modulate CVC during any concentration of SNP administration in older adults (all P>0.05). We show that during low dose NO administration (e.g., 0.005-0.05mM), KCa channels contribute to cutaneous blood flow regulation in young adults, however in older adults, COX inhibition increases cutaneous blood flow through a KCa channel-dependent mechanism.
- vascular smooth muscle cell
- endothelial cell
- Copyright © 2016, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology