Acute stress in rats produces a rapid and sustained increase in prostacyclin production in aortic tissue: Dependence on corticosterone

Abstract

Immobilization stress in rats is accompanied by a fast and transient increase in plasma catecholamines (CA) and a slow but more sustained increase in plasma corticosterone (CORT) levels. CA are reported to increase prostacyclin (PGI 2) secretion in endothelial cells in culture and in isolated vascular tissue. The present study was undertaken to determine a) whether short term immobilization stress in rats affects PGI 2 synthesis in aortic tissue and b) whether such effects are dependent on the maintenance of an intact hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats were immobilized for 5, 15 and 30 min., killed by a blow to the head and aortic rings immediately prepared and incubated in oxygenated Krebs-Ringer buffer at 37 °C. Secretion of PGI 2 was assessed by measuring the amount of 6-keto-PGF 1α, the stable hydrolysis product of PGI 2, formed in the incubation medium during 90 min. Rats immobilized for 15 min demonstrated a six to seven times increase in plasma ACTH and a more than ten times increase in plasma CORT levels. Aortic rings from stressed rats also demonstrated a significant and sustained (2 hours) increase in PGI 2 secretion when compared with tissue from unstressed rats (68 pg 6-keto-PGF 1α/mg tissue per min vs 35 pg 6-keto-PGF 1α/mg tissue per min during the first hour). Shorter (5 min) or longer (30 min) periods of stress gave comparable results. Adrenalectomy (ADX) carried out 7 days prior to immobilization, did not affect the baseline secretion of the eicosanoid, but completely prevented the increase in PGI 2 by immobilization stress. Administration of 2 μg/kg and 200 μg/kg i.a. of CORT to ADX-rats produced plasma levels of the hormone (36 ± 12 ng/ml and 934 ± 366 ng/ml respectively) comparable to those seen in unstressed and stressed rats. However only the higher dose of CORT when administered immediately prior to stress, restored the effect of immobilization stress on PGI 2 synthesis in aortic tissue of ADX-rats. Administration of the protein synthesis inhibitor cycloheximide (1 mg/kg) prior to stress did not affect the increase in PGI 2 secretion. In contrast to restraint stress, co-administration of ACTH and NE which also raised plasma levels of ACTH, CORT and NE to peak stress levels, did not increase prostacyclin production in aortic tissue. In conclusion, our findings demonstrate that short periods of immobilization stress produce a rapid and sustained increase in PGI 2 synthesis in the rat aorta, provided plasma levels of CORT are elevated. Since this permissive effect of CORT on stress induced prostacylin synthesis is rapid in onset, and insensitive to cycloheximide, it is probably mediated by a non-genomic mechanism. Although NE is known to activate PGI 2 synthesis in arterial tissue in vitro, the increase in aortic eicosanoid synthesis by stress does however not appear to be caused by a rise in plasma concentrations of NE.