Dopaminergic neuronal systems modulate the central cardiovascular effects of TRH in rats

Thyrotropin releasing hormone (pGlu-His-Pro-NH2-TRH) is a hypothalamic peptide that exerts pharmacological actions on the mammalian central nervous and circulatory systems independent of hormonal activity. In rats TRH produces an increase in blood pressure, heart rate and respiratory rate, following its intracerebroventricular (icv) administration. Because of a suspected role of the central dopamine (DA) system in these effects, we examined the influence of assorted DA receptor agonists and antagonists on the central cardiovascular and respiratory effects of TRH. Adult male Wistar rats were anesthetized with urethane (1.5 g/kg ip), implanted with an intracranial cannula for icv injections, and continuously monitored for (a) mean arterial blood pressure via an indwelling catheter in the right carotid artery, (b) heart rate via an ECG lead II signal and (c) respiratory rate via a photoelectric transducer. TRH (100 nmol) produced a sustained increase in blood pressure (ca. 20 mm Hg), heart rate (ca. 60 beats per min-bpm) and respiratory rate (< or = 200 breaths per min) during a 30 min observation period. The DA D1 receptor agonist SKF 38393 HCl (0.3 or 3.0 mg/kg ip) attenuated the effects of TRH on blood pressure and heart rate by > 50%, while the DA D2 receptor agonist quinpirole HCl (1.0 mg/kg ip) potentiated the chronotropic response to TRH by > 50%. The predominant DA D2 receptor antagonist haloperidol lactate (1.0 mg/kg ip) potentiated the effects of TRH on blood pressure and heart rate by > 50%, with the latter effect on heart rate being mimicked by the D2 receptor antagonist spiperone HCl (1.0 mg/kg ip). Chlorpromazine HCl (5.0 mg/kg ip), a low potency non-selective D2 receptor antagonist, had effects opposite to that of haloperidol. The effect of TRH on respiration was potentiated by quinpirole but not modified by other DA receptor agonists or antagonists. These findings indicate that the DA system is involved in a complex manner in the central cardiovascular actions of TRH, while DA D2 receptors alone appear to be involved in modulating respiratory effects of TRH.