Altered COX-mediated vasodilation across the menopause transition

The risk of cardiovascular disease increases in women following the menopause transition (MT), concurrent with worsening vascular endothelial function as characterized by decreased nitric oxide (NO)-mediated vasodilation. Concomitantly, cyclooxygenase (COX) metabolism appears to shift toward vasoconstrictor metabolites. Current research investigating mechanisms of vascular function across menopause has focused predominantly on large artery function and has compared hormone manipulation in young (~20 yrs) and older adults (>55 yrs) despite the fact that endothelial dysfunction manifests in the microvasculature across a narrower midlife age range (~40-60 yrs). Therefore, we investigated NO- and COX-mediated vasodilation in the cutaneous microvasculature in similarly-aged women surrounding the MT. We hypothesized that both NO- and COX-mediated vasodilation would be lower in postmenopausal (post) compared with premenopausal (pre) women. Pre (n = 3; 49±6 yrs) and post (n = 3; 57±1 yrs) women participated in non-invasive measurements of vascular function: flow-mediated dilation (FMD; primarily NO-mediated endothelium dependent vasodilation), anodal stimulation (AS; entirely COX-mediated vasodilation), and 39 (~95% NO-mediated vasodilation) and 42°C (~88% NO-mediated vasodilation) local heating (LH) protocols. For FMD, brachial artery diameter was imaged via ultrasound with edge-detection software. Baseline was recorded for 2 min. Forearm blood flow was occluded for 5 min, followed by a 4 min recovery period. %FMD = Δ diameter/baseline diameter. For AS, an iontophoresis unit was placed on the forearm where a laser Doppler flowmeter (LDF) probe was placed within the iontophoresis chamber. Following a 10 min baseline, a lactated Ringer’s dose-response stimulation protocol was utilized to increase local blood flow. For 39 and 42°C LH, 2 LH units with LDF probes were placed on the forearm. Standard LH protocols were conducted including 10-min baseline at 33°C, then one heater was set to 39°C and the other 42°C until a plateau in red cell flux occurred, then both were set to 43°C to normalize data to a site-specific maximum. For both AS and LH, continuous red blood cell flux was measured and divided by mean arterial pressure to calculate cutaneous vascular conductance (CVC). For LH experiments, CVC was recorded as a % of max (%CVCmax). While there were no differences between pre and post FMD (pre = 1.35% v post = 3.11%, p = 0.28) or in the 39°C (pre = 55% v post = 50%; p = 0.78) or 42°C heating responses (pre = 82% v post = 90%, p = 0.10), the CVC response to AS was greater in post (p = 0.03). COX-mediated dilation is increased in postmenopausal women in the cutaneous microvasculature independent of altered NO-mediated dilation or menopause—dependent changes in large artery function. These preliminary data suggest that alterations are evident in the role of COX but not NO in cutaneous microvascular function across the MT and perhaps altered mechanisms of FMD across this transition. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.