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Abstract
Chronic kidney disease (CKD) is considered a public health problem, assuming epidemic proportions worldwide. In this context, the preponderance of CKD prevalence in male over age-matched female patients is of note. In the present study, we investigated the impact of the gender on the development of experimental CKD induced by chronic nitric oxide (NO) inhibition in Wistar male and female rats through the administration of L-NAME. CKD model induced by L-NAME is characterized by systemic vasoconstriction, resulting in severe hypertension, albuminuria, renal ischemia, glomerulosclerosis, interstitial expansion, and macrophage infiltration. After 30 days of CKD induction, male NAME rats exhibited remarkable albuminuria, augmented cortical histological damage, interstitial inflammation, and fibrosis. Age-matched female NAME rats showed significantly lower albuminuria, diminished glomerular ischemia, and glomerulosclerosis, as well as a significant reduction in the expression of α-smooth muscle actin renal interstitial Ang II+ cells. Thus, the present study demonstrated that female rats submitted to the NAME model developed less severe CKD than males. Female renoprotection could be promoted by both the estrogen anti-inflammatory activity and/or by the lack of testosterone, related to renin-angiotensin-aldosterone system hyperactivation and fibrogenesis. However, the influence of sex hormones on the progression of CKD needs to be further investigated.
Highlights
In the last decades, chronic kidney disease (CKD) became a public health problem with epidemic proportions worldwide, with more than 2 million of patients requiring hemodialysis or other renal replacement therapy [1, 2]
There was no difference in the growth rate between male and female NAME rats induced by L-NAME
nitric oxide (NO) synthesis was chronically inhibited by the administration of L-NAME, an L-arginine analogue, in Wistar male and female rats
Summary
Chronic kidney disease (CKD) became a public health problem with epidemic proportions worldwide, with more than 2 million of patients requiring hemodialysis or other renal replacement therapy [1, 2]. The progressive feature of CKD represents an additional reason for addressing this disease as a serious public health concern nowadays In this context, the well-recognized preponderance of CKD prevalence in male over female patients is of note. The possible protective role of estrogens on the progression of renal disease is further evidenced by the lower prevalence of CKD in premenopausal women compared with age-matched men. This renoprotection observed in females disappears after the beginning of menopause, when the BioMed Research International estrogen serum levels decreases drastically, suggesting an important role of sexual hormones on the development of renal function loss [8,9,10]
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