Hypertensive disorders of pregnancy increase the likelihood for mortality in the pregnant mother and fetus and is also a predictor for future cardiovascular disease in these women and their offspring. As obesity is a leading risk factor for hypertensive disorders of pregnancy, it is critical to identify interventions, such as lifestyle modifications, that effectively reduce the risk for hypertension during pregnancy. This is especially the case because there are no steadfast pharmacological strategies available yet. Although there have been studies to suggest that moderate forms of exercise, like swimming, are safe and reduce the risk for hypertension during pregnancy, less is known about how swimming exercise impacts body weight, fat mass, and blood pressure levels in obese pregnancies. We previously characterized a rat model that is obese and hypertensive during pregnancy, namely the heterozygous melanocortin-4 receptor (MC4R)-deficient pregnant rat. Deficiency of MC4R causes hyperphagia and increased fat mass and body weight. Using this model, we tested the hypothesis that the physical exercise of swimming reduces body weight, fat mass, and blood pressure to a greater extent in obese versus lean pregnant rats. Rats were trained for ~5 days to the exercise protocol consisting of voluntary swimming for 20 min/day in water that was 32-35C. Timed-pregnancies were generated with genotype-matched males with gestational day 0 indicated by sperm in the vaginal smear. Rats were either allocated to the SWIM group from gestational day 1-19 or remained in the sedentary (SED) group. It was found that swimming significantly reduced (P <0.05) gestational weight gain in MC4R-def pregnant rats (SWIM: 37.2±17.6 g, N=11 vs. SED 53.5±14.9 g, N=13) but not wild-type (WT) controls (SWIM: 52.2±4.5 g, N=9 vs. SED: 51.4±11.7 g, N=11). Swimming slightly, but not significantly (P>0.05), increased cumulative food intake in both MC4R-def (SWIM: 346±59 g vs. SED: 311±22 g) and WT controls (SWIM: 343±29 g vs. SED: 314±23 g). The remaining outcomes were examined on gestational day 19. It was detected that swimming reduced (P <0.05) the elevated % total body fat mass (EchoMRI) in MC4R-def (SWIM: 14.7±2.1 % vs. SED: 17.7±2.3 %) but not WT controls (SWIM: 9.9±1.0 % vs. SED: 12.1±2.1 %). Furthermore, swimming reduced the higher circulating levels of the pro-hypertensive adipokine, leptin, only in MC4R-def (SWIM: 3.6±0.2 ng/mL vs. SED: 7.9±1.1 ng/mL) and not WT controls (SWIM: 2.2±0.2 ng/mL vs. SED: 3.4±0.3 ng/mL). Conscious blood pressure was determined using carotid catheters implanted on gestational day 18. The elevated absolute mean arterial blood pressure (MAP) levels were numerically, but not significantly (P>0.05), lowered by swimming exercise in MC4R-def (SWIM: 111±2 mmHg vs. SED: 120±12 mmHg) but not WT controls (SWIM: 109±9 mmHg vs. SED: 110±7 mmHg). However, it was determined that the % blood pressure lowering effect of swimming exercise was significantly greater (P <0.05) in MC4R-def (-7±1 %) compared to the WT controls (-1±2 %). Average fetal weights were not significantly different (P>0.05) between any of the groups for MC4R-def (SWIM: 1.9±0.2 g vs. SED: 2.0±0.1 g) or WT controls (SWIM: 1.9±0.2 g vs. SED: 2.1±0.2 g). Overall, these data indicate that swimming exercise is effective in reducing body weight and fat mass as well as having a greater impact to lower blood pressure in obese hypertensive pregnancies. P20GM121334