This study examines whether the intake of a high-fat diet very early in life leads to changes in arterial pressure and renal function and evaluates whether the mechanisms involved in these changes are sex-dependent. Experiments were performed in male and female Sprague-Dawley rats fed a normal or high-fat diet from weaning to 4 mo of age. This exposure to a high-fat diet lead to an angiotensin II-dependent elevation in arterial pressure and to significant increments in fat abdominal volume and plasma leptin that were similar in both sexes. In addition, the angiotensin II-induced increment in renal vascular resistance was greater ( P < 0.05) in male (106 ± 14%) and female (97 ± 15%) rats fed a high-fat diet than in rats fed a normal-fat diet (51 ± 8%). However, the high-fat intake during early life induced increments in albuminuria, interleukin-6, and infiltration of CD3 lymphocytes in the renal parenchyma that were greater ( P < 0.05) in male than in female rats. Other sex-dependent differences in response to high-fat intake were that adiponectin levels only decreased in females (21%, P < 0.05), and renal NF-κB expression only increased in males (31%, P < 0.05). In summary, the early exposure to a high-fat diet leads to angiotensin II-dependent arterial pressure elevations and to increments in abdominal fat and in the renal sensitivity to angiotensin II that are similar in both sexes. However, the mechanisms involved in the renal changes associated with early exposure to a high-fat diet are different in males and females.

Objective To examine whether the cardiac, renal and uterine physiological hemodynamic changes during gestation are altered in rats with an early and prolonged exposure to a high fat diet (HFD). Methods Arterial pressure and cardiac, renal, uterine and radial arteries hemodynamic changes during gestation were examined in adult SD rats exposed to normal (13%) (n = 8) or high (60%) (n = 8) fat diets from weaning. Plethysmography, high-resolution high-frequency ultrasonography and clearance of an inulin analog were used to evaluate the arterial pressure and hemodynamic changes before and at days 7, 14 and 19 of gestation. Results Arterial pressure was higher (P<0.05) in rats with high than in those with normal (NFD) fat diet before pregnancy (123 ±3 and 110 ±3 mmHg, respectively) and only decreased at day 14 of gestation in rats with NFD (98±4 mmHg, P<0.05). A significant increment in stroke volume (42 ±10%) and cardiac output (51 ±12%) was found at day 19 of pregnancy in rats with NFD. The changes in stroke volume and cardiac output were similar in rats with NFD and HFD. When compared to the values obtained before pregnancy, a transitory elevation in renal blood flow was found at day 14 of pregnancy in both groups. However, glomerular filtration rate only increased (P<0.05) in rats with NFD at days 14 (20 ±7%) and 19 (27 ±8%) of gestation. The significant elevations of mean velocity, and velocity time integral throughout gestation in radial (127 ±26% and 111 ±23%, respectively) and uterine (91 ±16% and 111 ±25%, respectively) arteries of rats with NFD were not found in rats with an early and prolonged HFD.

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Prolonged high fat diet (HFD) accelerates the cardiovascular, renal and metabolic dysfunction in hypertensive rats with altered renal development (ARDev). Soluble guanylate cyclase (sGC) stimulation or sodium-glucose cotransporter 2 (SGLT2) inhibition may improve cardiovascular, renal, and metabolic function in settings of hypertension and obesity. This study examined whether six weeks treatment with an SGLT2 inhibitor (EMPAGLIFLOZIN, 7 mg/kg/day) enhances the cardiovascular, renal and metabolic effects of a sGC stimulator (PRALICIGUAT, 10 mg/kg/day) in hypertensive rats with ARDev and prolonged exposure to HFD. Arterial pressure (AP), renal vascular resistance (RVR), fat abdominal volume (FAV), insulin resistance, leptin and triglycerides levels and intrarenal infiltration of inflammatory cells were higher, but cardiac output and creatinine clearance were lower in hypertensive rats (n=15) than in normotensive rats (n=7). PRALICIGUAT administration (n=10) to hypertensive rats reduced (P<0.05) AP, FAV, plasma concentrations of leptin and triglycerides, and increased (P<0.05) cardiac output and creatinine clearance. EMPAGLIFLOZIN administration (n=8) only increased (P<0.05) glucosuria and creatinine clearance, and decreased (P<0.05) plasma leptin and triglycerides concentrations in hypertensive rats. Simultaneous administration of PRALICIGUAT and EMPAGLIFLOZIN (n=10) accelerated the decrease in AP, improved glucose tolerance, reduced (P<0.05) incremental body weight gain, and decreased (P<0.05) insulin resistance index, RVR and the infiltration of T-CD3 lymphocytes in renal cortex and renal medulla. In summary, the combined administration of PRALICIGUAT and EMPAGLIFLOZIN leads to a greater improvement of the cardiovascular, renal and metabolic dysfunction secondary to prolonged exposure to HFD in hypertensive rats with ARDev than the treatment with either PRALICIGUAT or EMPAGLIFLOZIN alone.

Objective The aim of this study was to compare in vivo vs ex vivo liver stiffness in rats with acoustic radiation force impulse (ARFI) elastography using the histological findings as the gold standard. Methods Eighteen male Wistar rats aged 16–18 months were divided into a control group (n = 6) and obese group (n = 12). Liver stiffness was measured with shear wave velocity (SWV) using the ARFI technique both in vivo and ex vivo . The degree of fibrosis, steatosis and liver inflammation was evaluated in the histological findings. Pearson’s correlation coefficient was applied to relate the SWV values to the histological parameters. Results The SWV values acquired in the ex vivo study were significantly lower than those obtained in vivo ( P < 0.004). A significantly higher correlation value between the degree of liver fibrosis and the ARFI elastography assessment was observed in the ex vivo study (r = 0.706, P < 0.002), than the in vivo study (r = 0.623, P < 0.05). Conclusion Assessment of liver stiffness using ARFI elastography yielded a significant correlation between SWV and liver fibrosis in both the in vivo and ex vivo experiments. We consider that by minimising the influence of possible sources of artefact we could improve the accuracy of the measurements acquired with ARFI.