Sexual dimorphism in chloride transport in cultured rat aortic VSMCs.Sexual dimorphism in chloride transport in cultured rat aortic VSMCs.

Vascular reactivity differs between male and female rats, and estrogen antagonists may affect large conductance chloride channels. For these reasons we compared resting and AVP-stimulated chloride transport in primary cultures of aortae from 4 and 20 week Holtzman rats. Chloride analysis was done using MQAE. All buffers contained HCO3 and CO2. In cells from 4 week old rats (n = 26), resting Cli levels were higher (45 ± 8.7 mM) in male cells than in female cells (35 ± 8.8 mM, p < 0.001). The initial chloride efflux rate was higher in male 0.14 ± 0.06 than in female cells (0.044 ± 0.022 mMs−1, p < 0.001), and the elimination half life was shorter (4.0 ± 2.2 sec vs. 10.5 ± 3.5, p < 0.001). Influx in male cells (0.14 ± 0.04 mMs−1) also was higher than in female cells (0.08 ± 0.16, p < 0.001). In cells from mature (20 week) rats (n = 21) Cli was higher in male cells (52 ± 13, p < 0.05) than in male cells from immature males. Cli was similar in cells from immature and mature female rats (31 ± 8.8, p NS). Both initial influx and efflux rates in cells from 20 week old rats were higher than in cells from immature rats, and in the mature cells the sex difference was maintained for initial efflux and influx (p < 0.001), but not for half-life (p = 0.12), which was generally shorter in cells from mature rats. AVP (70 nM) added at time of exposure to zero chloride solution (4 week old rats, N = 17) augmented chloride efflux (male 0.24 ± 0.07, female 0.25 ± 0.09). The effect of AVP was much more pronounced in female cells than in male cells. The lower chloride transport parameters in female cells were dramatically reversed in cells from aortas of pregnant rats: Cli (56 ± 13 mM), efflux (0.35 ± 0.14) and influx (0.27 ± 0.07). Our results suggest that there is a very large sex difference in chloride transport in aortic VSMCs from both prepubertal and mature rats, the mechanism of which is unknown.