Gender differences in the renal changes induced by a prolonged high-fat diet in rats with altered renal development

Abstract

The mechanisms involved in renal dysfunction induced by high-fat diet (HFD) in subjects with altered renal development (ARDev) are understudied. The objective of this study is to examine whether there are sex-dependent differences in the mechanisms involved in the hypertension and deterioration of renal function in SD rats with prolonged HFD and ARDev. The role of angiotensin II (Ang II) in the arterial pressure (AP) increments, the renal hemodynamic sensitivity to Ang II, glomerular damage and changes in fat abdominal volume, plasma adipokine levels, renal NADPHp67phox expression, and renal infiltration of immune cells were examined. Hypertension and deterioration of renal function were enhanced (P < 0.05) in both sexes of rats with HFD and ARDev. The decrease (P < 0.05) of AP elicited by candesartan in hypertensive rats was similar to that induced by the simultaneous administration of candesartan and apocynin. The greater (P < 0.05) renal vasoconstriction induced by Ang II in both sexes of rats with HFD and ARDev was accompanied by an enhanced (P < 0.05) infiltration of CD-3 cells and macrophages in the renal cortex and renal medulla. The increments (P < 0.05) in the renal expression of NADPHp67phox and glomeruloesclerosis were greater (P < 0.05) in males than in females with HFD and ARDev. Our results suggest that the hypertension and deterioration of renal function induced by HFD in rats with ARDev are Ang II-dependent and mediated by increments in oxidative stress and immune system activation. Sex-dependent increments in oxidative stress and glomerular damage may contribute to the deterioration of renal function in these rats.

SGLT2 inhibition potentiates the cardiovascular, renal, and metabolic effects of sGC stimulation in hypertensive rats with prolonged exposure to high-fat diet

“…The increase in SAP elicited by the prolonged HFD in rats with ARDev had already been reported by our group ( 2 ) and is like that induced by HFD in rats with ARDev induced by prenatal dexamethasone ( 1 ). Prolonged exposure to HFD from an early age results in a further reduction of renal functional reserve in rats with ARDev and exposes the glomerulus to elevated renal perfusion pressures, with the consequent glomerular damage, the impairment of renal function and the exacerbation of hypertension ( 2 ).…”

“…The increase in SAP elicited by the prolonged HFD in rats with ARDev had already been reported by our group ( 2 ) and is like that induced by HFD in rats with ARDev induced by prenatal dexamethasone ( 1 ). Prolonged exposure to HFD from an early age results in a further reduction of renal functional reserve in rats with ARDev and exposes the glomerulus to elevated renal perfusion pressures, with the consequent glomerular damage, the impairment of renal function and the exacerbation of hypertension ( 2 ). This study examines to what extent modulating NO/sGC pathway attenuates the cardiovascular, renal, and metabolic effects of a prolonged HFD in rats with ARDev whose hypertension and deterioration of renal function are associated with a decrease in eNOS bioavailability and increases in oxidative and inflammatory markers ( 2 , 4 ).…”

“…Plasma samples were stored at −80°C. After that, rats were perfused with saline and formalin (30% PBS) to examine the T-CD3 lymphocytes and CD68 macrophages infiltration in the renal cortex and renal medulla ( 2 ).…”

“…Immunohistopathologic analyses of T-CD3 lymphocytes and CD68 macrophages infiltrates in the renal cortex and renal medulla were carried out as described ( 2 , 26 ), on 3-µm-thick sections from formalin-fixed and paraffin-embedded samples obtained from each group of rats. Polyclonal rabbit anti-T CD3 (dilution 1:500, Dako, A0452, Barcelona, Spain) or monoclonal rat anti-CD68 (dilution 1:100, Merck, MAB1435, Madrid, Spain) were first used.…”

“…Then, sections were incubated with a secondary anti-rabbit (Dako) or anti-rat (Vector, Madrid, Spain). Positive reaction was identified as described ( 2 , 26 ). Negative controls, obtained by incubating the samples only with dilution agent instead with the primary antibodies were also examined.…”