Ovine corticotrophin-releasing factor in dogs: dose-response relationships and effects of dexamethasone.

Abstract

Dose-response relationships between iv bolus injections (0, 0.1, 1 or 10 micrograms/kg) of synthetic ovine corticotropin-releasing factor (oCRF) and plasma immunoreactive (i) ACTH and cortisol concentrations were examined in healthy, conscious dogs. All doses of oCRF resulted in elevated plasma iACTH and cortisol levels over those of the controls. Maximum (or Peak) plasma iACTH concentrations were generally observed 20-30 min after oCRF and the magnitude of these peaks was a linear function (P less than 0.001) of the logarithm of the oCRF dose. The time of peak cortisol concentrations was more variable but the peak cortisol level was also linearly related (P less than 0.001) to the logarithm of the oCRF dose. An estimate for the response areas for both hormones demonstrated a quadratic (P less than 0.05) relationship with the logarithm of the oCRF dose. The relationship between oCRF and the iACTH response suggested a progressively greater response at increasing oCRF doses while a maximally effective oCRF dose was predicted in the cortisol response area relationship. Graded (0, 0.01, 0.1 or 1 mg/kg) bolus doses of dexamethasone produced a dose-dependent (P less than 0.03) decline in baseline plasma iACTH levels and a non-dose-dependent suppression in baseline plasma cortisol. Pretreatment with 0.001 mg dexamethasone/kg 4 or 8 h before injection of 1 microgram oCRF/kg did not alter the plasma iACTH or cortisol response; however, 0.1 mg dexamethasone/kg administered at these times totally abolished the responses to oCRF.(ABSTRACT TRUNCATED AT 250 WORDS)