Hypothyroidism attenuates SCH 23390-mediated depression of breathing and decreases d1 receptor expression in carotid bodies, PVN and striatum of hamsters

Hypothyroidism can lead to depressed breathing. We determined if propylthiouracil (PTU)-induced hypothyroidismin hamsters (HH) altered dopamine D1 receptor expression, D1 receptor-modulated ventilation, and ventilatory chemoreflex activation by hypoxia or hypercapnia. Hypothyroidism was induced by administering 0.04% PTU in drinking water for 3 months. Ventilation was evaluated following saline or 0.25 mg/kg SCH 23390,a D1 receptor antagonist, while awake hamsters breathed normoxic (21% O2 in N2), hypoxic (10% O2in N2) and hypercapnic (5% CO2 in O2)air. Relative to euthyroid hamsters (EH), HH exhibited decreased D1 receptor protein levels in carotid bodies, striatum, and hypothalamic paraventricular nucleus, but not in the nucleus tractus solitarius. Relative to EH, HH exhibited lower ventilation during exposure to normoxia, hypoxia, or hypercapnia, but comparable ventilatory responsiveness to chemoreflex activation. SCH23390 decreased ventilation of EH hamsters exposed to normoxia, hypoxia, and hypercapnia. In HH SCH23390 increased ventilation during baseline normoxia and did not affect ventilation during exposure to hypoxia and hypercapnia, resulting in reduced ventilatory responsivess to chemoreflex activation by hypoxia and hypercapnia. Furthermore, in HH D1 receptor protein levels are decreased in several brain regions and within the carotid bodies. Moreover, D1 receptor-modulation of breathing at rest and during gas exposures were depressed in EH but not HH.

Research highlights
► Hypothyroid hamsters exposed to air, hypoxia, and hypercapnia decreased ventilation.
► Blocking D1 receptors only decreased breathing in euthyroid hamsters.
► Hypothyroidism decreased D1 receptor protein in striatum, PVN and carotid bodies.
► Functional D1 receptor modulation of breathing is altered in hypothyroidism.