Sex Differences in Renal Inner Medullary ET‐1 Gene Expression Levels with Increasing Medullary Osmolality

Abstract

We previously reported that exposing the renal medulla to hyperosmotic solutions enhances urinary ET‐1 excretion in male rats. We have also seen that female rats have a more robust renal ET‐1 natriuretic capacity compared to males. Therefore, we determined whether intramedullary infusion of hyperosmotic saline has a differential effect on ET‐1 gene expression in inner medullas from anesthetized male and female rats. Isosmotic saline (284 mosmol/kgH2O) was infused into the renal medullary interstitium (500 μl/h) during a 60 min equilibration period and 30 min baseline urine collection period, followed by isosmotic or hyperosmotic saline (1800 mosmol/kgH2O) for two further 30 min periods. At the end of each experiment, the renal inner medulla was isolated for ET‐1 mRNA assessment using the real‐time quantitative polymerase chain reaction (RT‐PCR) technique. Compared with isosmotic saline, hyperosmotic saline infused in the renal medulla caused significant increases in urine flow in both male and female rats (from 6.3±0.9 to 12.2±1.7 and from 8.2±1.3 to 15.0±2.8 μl/min, respectively). Sodium excretion was also significantly enhanced, in both males and females (from 0.6±0.1 to 8.3±1.9 and from 0.9±0.2 to 5.8±1.0 μl/min, respectively). Inner medullary ET‐1 expression in male rats was significantly increased after 60 min of medullary interstitial infusion of hyperosmotic saline (from 1.0± 0.1 to 1.4± 0.1 fold change, p<0.05). In contrast, ET‐1 expression did not change with medullary hyperosmotic infusion in females. These data indicate that an increase in renal inner medullary ET‐1 could play a more important role in the diuretic and natriuretic response to intramedullary hyperosmolality in male compared to female rats.