title: Insulin, cortisol and catecholamines do not regulate circadian variations in fibrinolytic activity.
abstract: To evaluate possible hormonal regulators of the diurnal rhythm in fibrinolytic activity, we measured tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor activity (PAI-1), t-PA antigen, insulin, cortisol, and catecholamines in 6 healthy males (age 34 +/- 5) every 2 hours for 24 hours. Fibrinolysis was characterized by a peak in PAI-1 activity and a trough in t-PA activity at 0600 h. PAI-1 activity increased 92% and t-PA activity decreased 56% between 2400 h and 0600 h. t-PA antigen (principally a measure of t-PA/PAI-1 complex), peaked at 0800 h. In comparison, insulin levels were lowest at night when PAI-1 activity was rising. The weak inverse correlation between insulin and PAI-1 activity (r = -0.28, p less than 0.02), was not sufficient to explain the diurnal change in fibrinolysis. While cortisol demonstrated the expected circadian change, the increase in cortisol did not occur until 0400 h, 4-6 hours after the rise in PAI-1 and decrease in t-PA activity started. Supine resting plasma epinephrine and norepinephrine showed no circadian rhythm. From this data, we hypothesize that the increased level of PAI-1 in the morning consumes t-PA, leading to decreased t-PA activity and increased t-PA/PAI-1 complex. Further, we conclude that insulin, cortisol, and catecholamines are not responsible for the circadian rhythm of fibrinolysis.
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle 98195.
authors.forename: W L
authors.initials: WL
authors.lastname: Chandler
authors.forename: D
authors.initials: D
authors.lastname: Mornin
authors.forename: R O
authors.initials: RO
authors.lastname: Whitten
authors.forename: P
authors.initials: P
authors.lastname: Angleton
authors.forename: F M
authors.initials: FM
authors.lastname: Farin
authors.forename: T R
authors.initials: TR
authors.lastname: Fritsche
authors.forename: R C
authors.initials: RC
authors.lastname: Veith
authors.forename: J R
authors.initials: JR
authors.lastname: Stratton
mesh_terms: D000328:Adult; D002395:Catecholamines / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000502:physiology*; D007328:Insulin / Q000097:blood / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D015849:Plasminogen Inactivators / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D002395:Catecholamines; D007328:Insulin; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine