Sex Differences in the Diurnal Natriuretic Response to a Salt Load in Rats Lacking a Functional ETB Receptor

Abstract

Male rats lacking the ETB receptor (ETB def) exhibit salt‐sensitive hypertension due to impaired renal sodium handling. Given that females generally have a reduced incidence of salt‐sensitive hypertension compared to males, we hypothesized that female ETB def rats are better able to excrete a salt load compared to males. ETB def and genetic control rats of both sexes were implanted with telemetry transmitters to monitor mean arterial pressure (MAP) and given at least a week to recover. Following several days of baseline urine collection in 12 hr light/dark increments, rats were given a single 900µEq Na salt load (NaCl) by oral gavage at the beginning of their active (7pm‐7am, dark) or inactive (7am‐7pm, light) period. Urine was again collected in 12 hr intervals for several more days. We previously showed that ETB def males excrete significantly less salt during the initial 12 hr following an acute salt load whether given at the beginning of the active or inactive period compared to genetic controls, an effect that was more pronounced when the salt load was given prior to the inactive period. ETB def females excreted significantly more salt vs. ETB def males following the acute salt load given during the beginning of the active period (673 ± 111 vs. 320 ± 98µEq Na/12hr, P<0.05) and again showed an improved natriuresis vs. ETB def males following a salt load given at the start of the inactive period (183 ± 60 vs. 50 ± 91µEq Na/12hr). There was no significant effect of the salt loading on MAP in any group, although both male and female ETB def rats had significantly elevated MAP compared to controls. These data show that despite the loss of the ETB receptor, females excrete an acute salt load more efficiently than males.