Exercise Pressor Reflex is Preserved in Streptozotocin-Induced Female Type 1 Diabetic Rats

Type 1 diabetes (T1D) is associated with abnormal cardiovascular responses to exercise, driven in part by an exaggerated exercise pressor reflex. T1D also disrupts the cardioprotective effect of female sex hormones, particularly estrogens, thereby eliminating many of the advantages typically observed in healthy young females. The purpose of this study was to determine the exercise pressor reflex in female T1D rats immediately after developing diabetes and after the disease progressed for several weeks. Based on previous studies primarily in male rats, we hypothesized female T1D rats would exhibit an exaggerated exercise pressor reflex at early, but not late, stages of the disease compared to healthy controls. Experiments were performed on adult female Sprague-Dawley T1D or healthy rats. T1D was induced by intraperitoneal injection of streptozotocin (STZ), and terminal experiments were conducted at 1 week (early) and 4-6 weeks (late) after STZ or vehicle injection. Rats were considered diabetic if non-fasted blood glucose concentration exceeded 300 mg/dl. The exercise pressor reflex was evoked by statically contracting the skeletal muscle for 30s in unanesthetized, decerebrated rats. Pressor responses were calculated as the change (∆) in peak mean arterial pressure (MAP) during 30s of contraction relative to baseline. Estrous cycle phase was determined using vaginal smears and microscopic evaluation, while serum concentrations of estradiol, testosterone, and progesterone were quantified using radioimmunoassays or ELISAs. Data are presented as mean ± SD. Contrary to our hypothesis, MAP responses were similar between groups immediately after diabetes onset (T1D: ∆MAP: 13 ± 4 mmHg, n=10 and healthy: ∆MAP: 13 ± 4 mmHg, n=10; p=0.892), and remained similar after several weeks of disease progression (T1D: ∆MAP: 16 ± 7 mmHg, n=10 and healthy: ∆MAP: 12 ± 5 mmHg, n=7; p=0.206). At the early stage, heart rate (HR) responses were greater in T1D rats compared with healthy controls (T1D: ∆HR: 17 ± 10 bpm, n=10 and healthy: ∆HR: 5 ± 11 bpm, n=10; p=0.017), whereas no difference was observed at the late stage (T1D: ∆HR: 13 ± 13 bpm, n=10 and healthy: ∆HR: 7 ± 6 bpm, n=7; p=0.239). The tension developed during muscle contraction was similar between groups at both stages of the disease. All female rats exhibited a well-defined estrous cycle assessed by vaginal smear, with most in the diestrus phase on the day of the terminal experiment. No differences in estradiol or testosterone concentrations were observed between groups at either stage of the disease. Progesterone levels were similar between groups early in the disease (T1D: 44 ± 12 ng/mL and healthy: 49 ± 24 ng/mL; p=0.676) but were lower in T1D rats compared to healthy controls at later stages (T1D: 50 ± 20 ng/mL and healthy: 100 ± 52 ng/mL; p=0.016). These findings demonstrate that the exercise pressor reflex is preserved in female T1D rats. Because T1D does not affect sex hormone levels, the preserved reflex may be supported by progesterone, potentially acting with estrogen to maintain cardiovascular responses during muscle contraction. This project was supported by NIH R01HL 166323. 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.