seglitide and Hemorrhage

This study examines the effect of intracerebroventricular infusion of the 'superactive' somatostatin (SRIF) analogue cycl--(N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe) on the plasma adrenocorticotrophic hormone (ACTH) response to hemorrhage in conscious sheep. Hemorrhage (15 ml/kg over 15 min) increased plasma ACTH from 55 +/- 20 to 815 +/- 148 pg/ml at 30 min (p less than 0.001). Infusion of the SRIF analogue intracerebroventricularly at 0.08 microgram/min for 10 min prior to and for 60 min after commencement of hemorrhage resulted in a partial inhibition of the plasma ACTH response. Infusion of the analogue at 0.8 microgram/min blocked the increase in plasma ACTH at 30 min. Plasma ACTH was 21 +/- 3 pg/ml as control and 66 +/- 47 pg/ml at 30 min. The SRIF analogue had no effect on plasma ACTH in the same animals in control experiments with no hemorrhage. These studies suggest that SRIF may act as a central inhibitor of ACTH release. The mechanism by which the SRIF analogue inhibits ACTH secretion is unknown but could involve inhibition of corticotropin-releasing factor release and/or an inhibition of ACTH release from the pituitary gland. The route of administration of the SRIF analogue and the finding that the SRIF analogue did not prevent systemic corticotropin-releasing factor stimulation of ACTH suggest an effect of the SRIF analogue in the hypothalamus.

Topics: Adrenocorticotropic Hormone; Animals; Hemorrhage; Injections, Intraventricular; Peptides, Cyclic; Sheep; Somatostatin; Stress, Physiological