The progesterone receptor antagonist mifepristone abolishes carotid sinus nerve response to hypoxia in rat pups.

Abstract

We tested the hypothesis that endogenous progesterone enhances peripheral chemoreceptors function in rat pups. Newborn rats have been treated with the progesterone receptor antagonist mifepristone (Mif) between postnatal days 3‐12 (70μg/g/day) and compared to control (Cont). We used the in‐vitro carotid body/carotid sinus nerve (CSN) preparation to record CSN activity (impulses/sec) in 12‐day‐old rats under normoxia (perfusion medium bubbled with 21%O2‐5%CO2), in response to hypoxia (5%O2‐5%CO2), or nicotine (mediator between carotid body type I cells and CSN terminals, 100μM) supefusion for 3‐4 minutes each. Baseline CSN firing frequency was similar between groups, at 2.7±0.3 in Cont and 2.6±0.3 Hz in Mif pups. At steady state hypoxic CSN activity increased to 7.5±0.9 Hz in Cont, but was left unchanged in Mif pups (3.0±0.5 Hz, p<0.0002 between groups). In response to nicotine superfusion, CSN firing activity increased to 10.8±1.9 Hz in Cont and to 6.1±3.3 Hz in Mif (p<0.04 between groups). We conclude that endogenous progesterone plays an important role in carotid body during postnatal development in rats. Founded by SickKids Foundation (XG07‐006)