These studies define potential sites and mechanisms by which
thyrotropin releasing hormone (TRH) stimulates cardiorespiratory function in normotensive rats as well as in rats subjected to endotoxic
shock. Changes in mean arterial pressure, pulse pressure, heart rate, and respiratory rate were determined in conscious animals following injection of TRH into the lateral, third, or fourth ventricular spaces.
Injections of TRH into the third ventricular space resulted in a greater increase in cardiorespiratory variables than did fourth ventricular injection. In
endotoxin-treated rats, the cardiorespiratory effects of intracerebroventricular (icv) TRH and its analog
MK 771 were assessed. TRH and
MK 771 were shown to act within the brain to reverse endotoxic
shock hypotension; at the doses used, the pressor effects of these two tripeptides were achieved through selectively different actions upon heart rate and pulse pressure. Adrenal demedullated and
sham-operated control rats subjected to endotoxic
shock were injected with icv and intravenous (iv) TRH in order to evaluate the potential involvement of sympatho-medullary function in cardiorespiratory responses. The cardiovascular effects of icv TRH were dependent upon adrenal medullary integrity; effects of iv TRH were not. Doses of iv TRH which effectively reverse
shock neither altered nociceptive latencies nor interfered with
analgesic responses to
morphine. Collectively, these studies reinforce the potential therapeutic utility of TRH and its analogs in the treatment of
shock and indicate potential sites and mechanisms which mediate these salutary effects.