Testosterone Reduces mRNA Expression of Renal Sodium Transporters but does not Affect Blood Pressure During a Ten‐Day Angiotensin II Infusion Period in Castrated Mice

Abstract

Sex differences in blood pressure regulation are well known and it is widely accepted that premenopausal females are protected from hypertension and cardiovascular disease compared to age‐matched males. Despite extensive investigation, the effects of sex steroids on blood pressure and renal sodium handling remain debated. The purpose of this study was to determine the effects of testosterone administration on angiotensin II (Ang II) – induced increase in blood pressure and other physiological effects in castrated mice. Four‐week‐old CD‐1 castrated mice were obtained from Envigo Inc. (Indianapolis, IN) and placed in metabolic cages for a five‐day baseline period followed by implantation of an Alzet osmotic pump containing either vehicle or Ang II (1μg/kg/min) and either a placebo or 2.5 mg testosterone‐acetate pellet (Innovative Research of America, Sarasota, FL). Measurements were recorded daily in the five‐day baseline and ten‐day post‐implantation periods in three groups of mice: vehicle‐placebo (V‐P), Ang II‐placebo (Ang II‐P), and Ang II‐testosterone (Ang II‐T) (n=4/group). Mice consumed standard chow and water ad libitum throughout the study. Systolic blood pressure (SBP, mmHg) was determined daily with the tail‐cuff technique (Kent Scientific, Torrington, CT). At the end of the study, mice were sacrificed, kidneys were removed, and cortical tissue samples were processed for real‐time qtPCR to compare mRNA expression in fold difference (FD) of key sodium transporters. Ang II significantly increased blood pressure. The delta SBP (baseline vs Ang II periods) was not different between the Ang II‐P and Ang II‐T groups: (27.0 ± 4.5 vs 31.1 ± 5.9, respectively), and these values were not different from the delta SBP (27.7 ± 2.7) in intact male (IM) mice under the same Ang II conditions determined in a previous study (Rouch, A. el al. FASEB J, 2018, A 904.6). Ang II administration significantly increased water intake and urine flow rate compared to baseline periods in Ang II‐P & Ang II‐T mice with no differences between those two groups, and there was no difference among groups with respect to sodium excretion or sodium balance. Interestingly, renal cortical tissue samples from Ang II‐P mice had higher mRNA expression of ENaC (a,b, & g), NKCC, NCC, and NHE3 compared to those from Ang II‐T mice (FD: 0.7–2.5, p < 0.05). Tissue samples from V‐P mice expressed higher mRNA levels of ENaC (b& g), Na‐K ATPase‐a1, NCC, and NHE2 compared to samples from IM mice (FD: 1.7–2.5, p < 0.05). We conclude that testosterone does not affect the ten‐day Ang II‐induced increase in blood pressure in the CD‐1 mouse. Testosterone reduces mRNA expression of key renal sodium transporters. Physiological consequences of T‐induced changes in mRNA expression remain to be determined.Support or Funding InformationThis project was supported by the National Institute of General Medical Sciences of National Institutes of Health through Grant Number 8P20GM103447.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.