Hypothyroidism stimulates D2 receptor-mediated breathing in response to acute hypoxia and alters D2 receptors levels in carotid bodies and brain

Hypothyroidism can depress breathing and alter dopamine D2 receptor expression and function. We hypothesized that relative to euthyroid hamsters (EH), hypothyroid hamsters (HH) contain increased D2 receptors in brain regions associated with breathing and carotid bodies (CB), and that stimulation of D2 receptors would decease ventilation more in the HH compared to the EH. Hamsters were treated with vehicle, carmoxirile (peripherally acting D2 receptor agonist), or bromocriptine (central and peripherally acting D2 receptor agonist) and breathing was evaluated during exposure to air, hypoxia, and then air. HH exhibited increased D2 receptor protein levels in the striatum and CB, but decreased levels in the paraventricular hypothalamic nucleus. Relative to vehicle, carmoxirole and bromocriptine stimulated ventilation in the HH during and following exposure to hypoxia. Only bromocriptine depressed ventilation in the EH during and after exposure to hypoxia. Thus, hypothyroidism impacts the expression of D2 receptors in the carotid body, PVN and striatum, and D2 stimulation affects ventilation remarkably differently than in EH.

► Hypothyroidism affects expression of D2 receptors in the PVN, stratum and CB.
► D2 receptor stimulation and hypoxia depressed breathing in normal hamsters.
► D2 receptor stimulation and hypoxia stimulated breathing in hypothyroid hamsters.
► Carotid body and CNS D2 modulation of breathing are altered in hypothyroidism.