Estrous cycle stage does impact the blood pressure response to treadmill exercise in female rats with simulated peripheral artery disease

Peripheral artery disease (PAD) is a common vascular disease induced by atherosclerotic plaque build-up in peripheral blood vessels. A hallmark of PAD is an exaggerated blood pressure (BP) response to exercise which is clinically significant because it increases a patients’ risk of stroke, fibrillation, and other vascular injuries. We recently reported that, compared to control rats, the BP response to treadmill exercise was exaggerated in male and female rats with simulated PAD induced by chronic femoral artery ligation. In “ligated” female rats, however, we did not control for estrus cycle stage and thus it is unknown if cycle stage influenced the magnitude of the exaggerated BP response to exercise. This is important because previous work has shown that reproductive cycle stage impacts the exercise pressor reflex, an important autonomic reflex that contributes to increased blood pressure during exercise. Therefore, we tested the hypothesis that estrous cycle stage would impact the magnitude of the exaggerated blood pressure response to treadmill exercise in female rats with chronically ligated femoral arteries. Methods: Fifty-two intact young adult (~12 weeks old) female rats had both femoral arteries ligated (6-0 suture) ~72 hours prior to the experiment. On experiment day, the right carotid artery was cannulated (PE-50) for BP measurement and blood sampling and exteriorized at the back of the neck. After recovery (~2 hrs), rats completed a 4 min treadmill exercise bout (15 m/min, 1° incline). Prior to the end of exercise, arterial blood was sampled for measurement of lactate (mmol/l) and glucose (mg/dl). After exercise, rats were anesthetized and vaginal lavage was performed for estrous cycle stage determination via cytology by at least two investigators independently. The pressor response to treadmill exercise, lactate and glucose were compared across cycle stages (diestrus: n=11, estrus: n=16, metestrus: n=12, and proestrus: n=14). The time courses of the systolic, mean, and diastolic BP response to exercise were compared across cycle stages with mixed two-way ANOVA. Glucose and lactate were compared across cycle stages with one-way ANOVA. Statistical significance was defined as P≤0.05. Results: There was no significant main effect of cycle stage (P-value range: 0.330-0.573) or interaction between time and cycle stage (P-value range: 0.071-0.171) for the time course of increase in systolic, diastolic, or mean arterial BP response to exercise. Likewise, estrus cycle stage had no effect on exercising blood lactate (diestrus: 1.3±0.1 mmol/L, estrus: 1.4±0.1 mmol/L, metestrus: 1.5±0.3 mmol/L, proestrus: 1.6±0.3 mmol/L, P=0.703) or glucose (diestrus: 112±8 mg/dL, estrus: 104±4 mg/dL, metestrus: 113±6 mg/dL, proestrus: 108±6 mg/dL; P=0.685). Conclusions: The data indicate that estrus cycle stage, and thus naturally occurring fluctuations in estrogen, in intact young adult female rats with ligated femoral arteries does not affect the exaggerated BP response to treadmill exercise. Funding: National Institutes of Health R01HL161160 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.