[Studies on the influence of releasing hormones TRH and CRH on respiratory regulation]

Patterns of neuroanatomical distribution of Thyrotropin-releasing hormone (TRH) and Corticotropin-releasing hormone (CRH) and of their receptors in brain areas of humans and of animals suppose a regulating function of both peptides on regulation of respiration. In experimental animals TRH induces rhythmical and synchronous firing of defined neurons of nucleus tractus solitarii. In fetal sheep, endogenous and exogenous CRH promotes maturation of breathing rhythm genesis. In own human studies we demonstrated a modulation of respiration in healthy test-subjects - predominantly a stimulation of respiration - by systemic TRH and CRH. This effect persists also during hypercapnia, as we showed in patients and in 12 healthy test subjects while re-breathing CO2: when compared to placebo, CRH i.v. (200 micrograms. Bissendorf, Hannover, FRG) induces a significant (p less than 0.0001) shift of the ventilatory response curve to the left (petCO2 vs minute volume). Stimulation of respiration by CRH is independent of activation of the pituitary-adrenal axis. At present two analogues of CRH are available for application in humans (as a diagnostic of endocrinological disorders): human CRH and ovine CRH. Both analogues are comparably effective in stimulation of ventilation although sequence of effects is different in both analogues. We also evaluated the effect of CRH in 10 aged patients who were under prolonged respirator therapy after major abdominal surgery; both human and ovine CRH (100-200 micrograms i.v.) induced a profound and long lasting stimulation of ventilation under assisted respirator therapy. Vigilance was also markedly increased in all patients and thus was of therapeutic value. CRH also has a potential to alter sleep architecture in healthy and in diseased persons.(ABSTRACT TRUNCATED AT 250 WORDS)