Sex-related Differences in the Glomerulus and Interstitium in Two-kidney, One-clip Hypertensive Rats

Arterial hypertension is a common medical condition worldwide and an important predictor of several complicated diseases that can lead to death if not treated. Several factors contribute to the development of arterial hypertension, including physiological, genetic, and lifestyle causes.

Among the constituents that regulate blood pressure, the Renin-Angiotensin-Aldosterone System (RAAS) is one of the most important. This hormonal mechanism controls the hemodynamic stability by adjusting blood pressure, fluid volume, and sodium-potassium balance. As well the RAAS is influenced in a way it functions by many agents such as sex hormones, particularly estrogen. Sex hormones modulate the RAS in various ways and consequently, the RAS displays significant sex-related differences. Estrogen acts on the multiple systems and mechanisms that influence blood pressure (BP) resulting in a decrease or increase of synthesis of different components of the RAAS depending of the sex and the pre or postmenopausal period.

Objective: The aim of this study was to examine if the renal glomerulus and tubulointerstitial injury in 2K1C male rats is greater than the female rats. Additionally, if ovariectomized rats show differences in the degree of renal injury than the 2K1C female rats.

Methods: Thirty-two animal rats were used in the study. The left renal artery of 3 male rats and 4 female rats were clipped in order to develop hypertension and later on develop injury in the renal glomerulus and tubulointerstitial so that the tissues could be mounted onto a histological slide and labeled with a CD68 antibody to be later analyzed under the microscope.

Results: The glomeruli and tubulointerstitial inflammation with macrophage infiltration were more severe in the non-clipped kidneys from female 2K1C rats compared to the ones from male and ovariectomized rats. The clipped kidneys from female 2K1C rats in the glomeruli showed an increase in inflammation and macrophage infiltration compared with the clipped kidneys from male and ovariectomized 2K1C rats with not statistical meaning. But non-clipped kidney from female was significantly greater compared with non-clipped kidney from ovariectomized rats (p < 0.05). Tubular macrophage infiltration in non-clip female rats was greater compared with male and ovariectomized rats but was not statistical meaningful. Overall, we observed that in the glomerulus as well as in the tubulointertitial, the non-clipped kidneys in both sexes showed a great inflammation with macrophage than in the clipped kidneys.

Conclusion: our experiment did not verify our hypothesis in regard to the expression of hypertension in female rats as opposed to males and ovariectomized rats. Surprisingly, our results showed that glomeruli and tubulointerstitial inflammation with macrophage infiltration were more severe in the non-clipped kidneys from female 2K1C rats showing that renal hypertension was higher in female 2K1C rats than male and ovariectomized rats.