Dopaminergic neuronal systems modulate the central cardiovascular effects of TRH in rats
Jedrusiak, J.; Brus, R.; Kostrzewa, R.M.; Słowiński, Z.
Polish Journal of Pharmacology 47(1): 43-52
1995
ISSN/ISBN: 1230-6002 PMID: 7550548 Document Number: 919
Thyrotropin releasing hormone (pGlu-His-Pro-NH-2 - 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 ( ltoreq 200 breaths per min) during a 30 min observation period. The DA D-1 receptor agonist SKF 38393 HC1 (0.3 or 3.0 mg/kg ip) attenuated the effects of TRH on blood pressure and heart rate by gt 50%, while the DA D-2 receptor agonist quinpirole HC1 (1.0 mg/kg ip) potentiated the chronotropic response to TRH by gt 50%. The predominant DA DA-2 receptor antagonist haloperidol lactate (1.0 mg/kg ip) potentiated the effects of TRH on blood pressure and heart rate by gt 50%, with the latter effect on heart rate being mimicked by the D-2 receptor antagonist spiperone HC1 (1.0 mg/kg ip). Chlorpromazine HC1 (5.0 mg/kg ip), a low potency non-selective D-2 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 D-2 receptors alone appear to be involved in modulating respiratory effects of TRH.
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