Estrogen But Not Androgen Plays an Important Role in Cardiovascular Function in DOCA-salt Mice

We previously reported that DOCA-salt treatment promotes exacerbated hypertension and cardiac dysfunction in male mice compared to females, which is associated with sex-dependent changes in miRNA in the brain. In this study, we investigated the role of sex hormones in these phenotypes. C57BL6/J mice (males and females, 20 weeks, n = 8-15) underwent uninephrectomy, followed by ovariectomy (OVX) or orchidectomy (OCX). Telemetry probes implantation (HD-X10) was performed for conscious blood pressure (BP) monitoring. After baseline recording, a DOCA pellet (50 mg, 21 days) was implanted subcutaneously and drinking water was replaced by 1% NaCl solution to induce salt sensitive hypertension. BP was recorded once weekly (24 hours) for 3 weeks. Cardiac function was assessed by echocardiography, and body weight, heart weight and kidney weight were measured at the end of the study. As observed previously, baseline systolic BP (SBP) was not different between female and male sham groups (Active phase: 126.9 ± 2.5 vs. 131.3 ± 2.3 mmHg) but higher in male than female shams following DOCA-salt treatment for 3 weeks (173.0 ± 5.1 vs. 154.2 ± 6.8 mmHg vs. p<0.05). Interestingly, in female mice, although baseline SBP was not different between OVX and sham groups, SBP was significantly higher in OVX (181.8 ± 3.7 mmHg, p<0.05 vs. sham) following DOCA-salt treatment. In addition, at 3 weeks of DOCA-salt treatment, left ventricular diastolic dysfunction was worse in OVX compared to sham females, as shown by higher E/E’ (38.3 ± 1.9 vs. 30.3 ± 1.5; p<0.05), while ejection fraction was not different between the 2 groups (75.5 ± 4.2 % vs. 73.7 ± 2.3%). Moreover, survival rate was reduced (77.8% vs. 100%), with higher heart weight (9.6 ± 0.6 vs. 7.3 ± 0.2m g/mm, p<0.05) and kidney weight (21.2 ± 1.5 vs. 14.4±0.5 mg/mm, p<0.001) observed in OVX compared to shams. In male mice, baseline BP was significantly reduced in OCX mice (119.5 ± 1.7 mmHg, p<0.05) compared to sham males. However, following DOCA-salt treatment, SBP was not different in OCX mice (169.0 ± 5.9 mmHg) compared to sham males, with no differences in E/E’ (33.8 ± 3.1 vs. 33.4 ± 1.8), survival rate (77.8% vs. 80%), heart weight (10.4 ± 0.5 vs. 9.1 ± 0.5 mg/mm) or kidney weight (18.0 ± 0.5 vs. 17.5 ± 0.9 mg/mm) observed in these 2 groups. These data suggest that estrogens protect females from developing hypertension and cardiac dysfunction while removing them increase the sensitivity to these diseases in females. On the contrary, testosterone has little effect on BP regulation and cardiac function in DOCA-salt hypertension. In conclusion, estrogens but not androgens play an important role in the regulation of BP and cardiac function in DOCA-salt hypertension. This work was supported in part by a research grant from the National Institutes of Health (HL163588). This abstract was presented at the American Physiology Summit 2025 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.