Administration of Prostacyclin Mediates Cutaneous Vasodilation but not Sweating in Young and Older Females: Roles for Nitric oxide and KCa channels

Abstract

Our recent report indicated that although prostacyclin does not mediate sweating in young and older males, it does modulate cutaneous vasodilation in both groups to a similar extent (Fujii et al. J Physiol 594 (21), 6419–6429, 2016). The same study also suggested that nitric oxide synthase (NOS) and calcium‐activated potassium (KCa) channels contribute to the prostacyclin‐induced cutaneous vasodilation in young males but, these contributions are diminished in older males. In our current study, we sought to evaluate whether the same responses are observed in young and older females. In young (25±4 years) and older (60±6 years) females (10 per group), cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites: 1) Control, 2) 10 mM L‐NNA, a non‐specific NOS inhibitor, 3) 50 mM tetraethylammonium (TEA), a non‐specific KCa channel blocker, and 4) 10 mM L‐NNA + 50 mM TEA. All fours sites were co‐administered with prostacyclin in an incremental manner (0.04, 0.4, 4, 40, 400 μM each for 25 min). Our results demonstrated that both NOS and/or KCa channels contribute to prostacyclin‐induced cutaneous vasodilation for young and older females. This is based on our observations that the increased CVC due to prostacyclin administration was attenuated by TEA (0.4 μM) and a combination of L‐NNA and TEA (at all concentrations tested) in young females. Additionally, in older females the increased CVC due to prostacyclin administration was also reduced by separate administration of either L‐NNA or TEA (0.04–4 μM), and a combination of both agents (0.04–40 μM) (all P≤0.05). Surprisingly, increases in CVC in response to 0.04–4 μM prostacyclin were greater in older relative to young females (all P≤0.05), and these age‐related differences were diminished when both L‐NNA and TEA were simultaneously administered (all P>0.05). No effect on sweat rate was observed in either group (all concentrations, P>0.05). We conclude that while prostacyclin does not mediate sweating, it modulates cutaneous vasodilation to a greater extent in older relative to young females. Wherein, this modulation is likely due to NOS‐ and KCa channel‐dependent mechanisms.Support or Funding InformationThis study was supported by the Natural Sciences and Engineering Research Council of Canada (Discovery grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014). Funds held by Dr. Glen P. Kenny.