Characterization of Sucrose-Induced Hypertension Model in Mice

Sucrose is a disaccharide composed of glucose and fructose, and is the primary component of table sugar. We previously reported that mice drinking 2% sucrose water develop hypertension accompanied by vascular remodeling. However, the detailed mechanisms and effects on other organs remain unclear. While sucrose is broken down into glucose and fructose and absorbed into the body, the effects of these components on blood pressure regulation have not been extensively studied. Therefore, we examined the effects of these sweeteners on cardiac function, insulin resistance, and sympathetic nerve activity. We hypothesized that sucrose induces insulin resistance and increased sympathetic nervous system activity, thereby raising blood pressure. We also hypothesized that sucrose causes not only vascular but also cardiac remodeling. Eight- to nine- week-old male C57BL6 mice were given drinking water sweetened with 2% sucrose, 4% glucose, or 4% fructose, or normal unsweetened water. Blood pressure was monitored for 4 weeks using a tail-cuff blood pressure monitoring system, and the mice were euthanized at the end of the 4th week. Echocardiography was performed before the start of drinking water, and at 2 and 4 weeks after initiation. The 4% glucose water group showed a significant increase in water intake compared with the control group. Estimated daily consumption of sucrose, glucose and fructose per body weight were 5.53 g/kg/day, 15.10 g/kg/day, and 10.65 g/kg/day, respectively. The systolic blood pressure of mice drinking 2% sucrose water was significantly higher than that of mice drinking normal water, starting on day 3 and continuing until the mice were euthanized on day 28 (systolic blood pressure 160.3 ± 4.8 vs 122.0 ± 1.3 mmHg, day28, p < 0.01). In contrast, systolic blood pressure did not increase in mice given 4% glucose (120.8 ± 7.5 mmHg, day28) or 4% fructose water (121.7 ± 2.3 mmHg, day28). Sucrose treatment increased interventricular septal thickness compared to normal water drinking mice (systolic: 1.314 ± 0.024 vs 1.150 ± 0.017 mm, day28, p < 0.01, diastolic: 0.913 ± 0.018 vs 0.827 ± 0.014 mm, day28, p < 0.01). Furthermore, although ejection fraction and fractional shortening were significantly reduced in the sucrose group, they remained within the normal range (ejection fraction: 54.14 ± 0.64 vs 59.59 ± 1.15 %, day28, p < 0.05, fractional shortening: 27.38 ± 0.45 vs 31.07 ± 0.81 %, day28, p < 0.05). Sucrose treatment increased fibrotic area around coronary arteries compared with the normal water group (0.711 ± 0.120 vs 0.345 ± 0.042, day28, p < 0.05). There was no significant difference in body weight, heart weight, or blood glucose levels among all treatment groups. However, serum insulin levels were significantly higher in the sucrose group but not glucose or fructose group. Serum norepinephrine concentrations showed no change among all treatment groups. We conclude that in addition to promoting hypertension and vascular remodeling, sucrose induces hyperinsulinemia, cardiac perivascular fibrosis, and moderate cardiac hypertrophy in mice. Our data further suggest that these effects are not mediated by glucose or fructose. While insulin resistance is considered one possible mechanism, further detailed investigation of the molecular mechanisms seems necessary. 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.