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Background Pulmonary arterial hypertension (PAH) is a progressive and fatal disease, leading to right ventricular (RV) dysfunction and death. PAH occurs ~4 fold more frequently in women than men; however, women with PAH exhibit better RV function and survival than men. Despite available treatments, PAH remains incurable and progressive. Novel and more effective therapeutics are urgently needed to treat PAH. PAH is also associated with involvement of other organs such as the kidney, which may in turn affect the lungs and RV. Sex differences and the associated mechanism in both RV and kidney in PAH are not well understood. This study aimed to characterize sex-dependent RV and renal remodelling in PAH.Methods Sugen-Hypoxia (SuHx) rat model of PAH was used to assess RV pressure-volume, mitochondrial function, heart weight, cardiomyocyte size, RV interstitial fibrosis, RCA remodelling and perivascular fibrosis, and kidney interstitial and perivascular fibrosis, vascular remodelling and occlusion and glomerular injury, using right heart cauterization, confocal microscopic imaging, and histological analysis as appropriate.Results SuHx caused significant increases in RV systolic pressure (RVSP) and RV hypertrophy in both sexes. However, female RV displayed a greater increase in cardiomyocyte size in response to SuHx compared with the males. SuHx caused a significant increase in RV end-diastolic pressure in males but not in females, and this is associated with significantly higher amount of RV interstitial fibrosis in the males than in the females in response to SuHx. While RCA intima-media thickness did not change in response to SuHx in either sex, RCA perivascular fibrosis significantly increased in male SuHx rats but not in females, and this is associated with impaired RV mitochondrial function (decreased mitochondrial fusion, membrane potential and superoxide) in male SuHx rats but preserved RV mitochondrial function in the females. Finally, SuHx resulted in a significant decrease in RV-pulmonary artery (RV-PA) coupling in males only, whereas in females RV-PA coupling was preserved. In kidney, SuHx caused a significant increase in both interstitial and perivascular fibrosis in both sexes. SuHx also significantly increased vascular intima-media thickness in both sexes. Finally, SuHx increased the percentage of arteriolar occlusion and glomerular injury in both sexes, but with lower percentages of arteriolar occlusion in male versus female controls and a greater increase in arteriolar occlusion in male SuHx (4-fold) compared with female SuHx (2-fold).Conclusions SuHx led to increased RV afterload in both sexes. However, compared with males, the females displayed distinct RV response with a greater cardiomyocyte hypertrophy, less fibrosis and preserved mitochondrial and RV function, and also distinct kidney response with less increase in arteriolar occlusion, which is associated with preserved RV function. Future studies investigating the underlying mechanism are needed to provide therapeutic insights into RV and kidney adaption in PAH.