title: 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 (PGI2) 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 PGI2 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 degrees C. Secretion of PGI2 was assessed by measuring the amount of 6-keto-PGF1 alpha, the stable hydrolysis product of PGI2, 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 PGI2 secretion when compared with tissue from unstressed rats (68 pg 6-keto-PGF1 alpha/mg tissue per min vs 35 pg 6-keto-PGF1 alpha/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 PGI2 by immobilization stress. Administration of 2 micrograms/kg and 200 micrograms/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 PGI2 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 PGI2 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 PGI2 synthesis in the rat aorta, provided plasma levels of CORT are elevated.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: UCB-Pharma R&D, Braine l'Alleud, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Grimée
authors.forename: E
authors.initials: E
authors.lastname: Wülfert
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000208:Acute Disease; D000311:Adrenal Glands / Q000502:physiology / Q000601:surgery; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood* / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015121:6-Ketoprostaglandin F1 alpha; D000324:Adrenocorticotropic Hormone; D003513:Cycloheximide; D011464:Epoprostenol; D003345:Corticosterone; D009638:Norepinephrine