Greater natriuretic response to ENaC inhibition in male versus female Sprague-Dawley rats

被引:13
|
作者
Soliman, Reham H. [1 ]
Johnston, Jermaine G. [1 ]
Gohar, Eman Y. [1 ]
Taylor, Crystal M. [1 ]
Pollock, David M. [1 ]
机构
[1] Univ Alabama Birmingham, Dept Med, Div Nephrol, Sect Cardiorenal Physiol & Med, 720 20th St S Kaul 802B, Birmingham, AL 35233 USA
关键词
circadian; diuresis; epithelial sodium channel; natriuresis; sex differences; EPITHELIAL NA+ CHANNEL; SALT-SENSITIVE HYPERTENSION; B RECEPTOR FUNCTION; BLOOD-PRESSURE; SODIUM-TRANSPORT; FLOW REGULATION; ALPHA-ENAC; BETA-ENAC; SKIN NA+; ENDOTHELIN;
D O I
10.1152/ajpregu.00060.2019
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Genes for the epithelial sodium channel (ENaC) subunits are expressed in a circadian manner, but whether this results in time-of-day differences in activity is not known. Recent data show that protein expression of ENaC subunits is higher in kidneys from female rats, yet females are more efficient in excreting an acute salt load. Thus, our in vivo study determined whether there is a time-of-day difference as well as a sex difference in the response to ENaC inhibition by benzamil. Our results showed that the natriuretic and diuretic responses to a single dose of benzamil were significantly greater in male compared with female rats whether given at the beginning of the inactive period [Zeitgeber time 0 (ZT0), 7 AM] or active period (ZT12, 7 PM). However, the response to benzamil was not significantly different between ZT0 and ZT12 dosing in either male or female rats. There was no difference in renal cortical alpha-ENaC protein abundance between ZT0 and ZT12 or males and females. Given previous reports of flow-induced stimulation of endothelin-1 (ET-1) production and sex differences in the renal endothelin system, we measured urinary ET-1 excretion to assess the effects of increased urine flow on intrarenal ET-1. ET-1 excretion was significantly increased following benzamil administration in both sexes, but this increase was significantly greater in females. These results support the hypothesis that ENaC activity is less prominent in maintaining Na+ balance in females independent of renal ET-1. Because ENaC subunit genes and protein expression vary by time of day and are greater in female rat kidneys, this suggests a clear disconnect between ENaC expression and channel activity.
引用
收藏
页码:R418 / R427
页数:10
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