Effects of gonadectomy and testosterone treatment on aquaporin expression in the kidney of normotensive and hypertensive rats

Abstract

We tested the hypothesis that testosterone-induced increase in blood pressure was due to changes in aquaporin (AQP) expression in kidneys. In this study, expression level of kidney AQPs was investigated under testosterone influence. Adult normotensive Wistar Kyoto (WKY) and hypertensive SHR male and female rats underwent gonadectomy. For female rats, testosterone was given for six weeks duration, two weeks following ovariectomy via subcutaneous silastic implant. Mean arterial pressure (MAP) was measured in all the rats after eight weeks via carotid artery cannulation and the rats were then sacrificed and kidneys were harvested for analyses of AQP-1, 2, 3, 4, 6, and 7 mRNA and protein expressions by quantitative real-time PCR and Western blotting, respectively. Distribution of AQP subunits' protein in kidneys was observed by immunofluorescence. In male WKY rats, MAP, AQP-1, 2, 4, and 7 protein; and mRNA expression decreased however AQP-3 protein and mRNA expression increased following orchidectomy. The vice versa effects were observed in testosterone-treated ovariectomized female WKY rats. However, no changes in AQP-6 expression were observed. Meanwhile, in adult male SHR rats, MAP and expression level of all AQP subunits decreased following orchidectomy. The opposite effects were seen in ovariectomized female SHR rats following testosterone treatment. Immunofluorescence study showed AQP-1 and AQP-7 were distributed in the proximal convoluted tubules (PCT) while AQP-2, AQP-4, and AQP-6 were distributed in the collecting ducts (CDs). AQP-3 was distributed in the PCT and CD. In conclusion, changes in AQP subunit expression in kidneys could explain changes in blood pressure under testosterone influence. Impact statement This study provides fundamental understanding on the mechanisms underlying testosterone-induced increase in blood pressure which involve regulation of aquaporin channel subunits in the kidneys. A better understanding of this issue can help to explain the reason for higher blood pressure in males as compared to females and may explain the reason for higher blood pressure in females after menopause than females before menopause, the former most probably related to the changes in female androgen.

Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role

“…Recently, Vasavan et al (2020) observed the same alterations in urea and creatinine with ND treatment. In this respect, Loh et al (2017) demonstrated that the elevated testosterone associated with AASs use increased the expression of aquaporins (AQPs) two four, and six in the collecting duct and AQPs-1 and sevene in the proximal convoluted tubule, consequently raised blood pressure, and increased water reabsorption resulting in hypertension and chronic kidney disease. Besides, AASs-induced direct glomerular toxicity due to increased body mass and glomerular hyperfiltration has been suggested as injury mechanisms (Parente Filho et al, 2020).…”

miRNAs as Novel Biomarkers of Chronic Kidney Injury in Anabolic-Androgenic Steroid Users: An Experimental Study

“…A direct relationship between AAS use and kidney injury has been described in several animal studies. High levels of several cytokines (such as TNF-α) ( Patil et al., 2016 ) and hypertension can cause the development of glomerulosclerosis ( Doublier et al., 2011 ), generating injuries similar to CKD ( Loh et al., 2017 ). CKD is caused by the progressive development of glomerular fibrosis or glomerulosclerosis, interstitial fibrosis, consequent atrophy, loss of tubular epithelium, and chronic inflammation, also with the loss of the peritubular capillaries that causes a decrease in the glomerular filtration rate ( Nogueira et al., 2017 ).…”

Sex Differences in Renal Function: Participation of Gonadal Hormones and Prolactin

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