title: Effects of nonspecific beta-adrenergic stimulation and blockade on blood coagulation in hypertension.
abstract: A hypercoagulable state might contribute to increased atherothrombotic risk in hypertension. The sympathetic nervous system is hyperactive in hypertension, and it regulates hemostatic function. We investigated the effect of nonspecific beta-adrenergic stimulation (isoproterenol) and blockade (propranolol) on clotting diathesis in hypertension. Fifteen hypertensive and 21 normotensive subjects underwent isoproterenol infusion in two sequential, fixed-order doses of 20 and then 40 ng. kg(-1). min(-1) for 15 min/dose. Thirteen subjects were double-blind studied after receiving placebo or propranolol (100 mg/day) for 5 days each. In hypertensive subjects, isoproterenol elicited a dose-dependent increase in plasma von Willebrand factor (vWF) antigen [F(2,34) = 5.02; P = 0.032] and a decrease in D-dimer [F(2,34) = 4.57; P = 0.040], whereas soluble tissue factor remained unchanged. Propranolol completely abolished the increase in vWF elicited by isoproterenol [F(1,12) = 10.25; P = 0.008] but had no significant effect on tissue factor and D-dimer. In hypertension, vWF is readily released from endothelial cells by beta-adrenergic stimulation, which might contribute to increased cardiovascular risk. However, beta-adrenergic stimulation alone may not be sufficient to trigger fibrin formation in vivo.
authors.affiliation: Department of Psychiatry, University of California, San Diego, California 92093, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: von Kanel
authors.forename: Joel E
authors.initials: JE
authors.lastname: Dimsdale
authors.forename: Karen A
authors.initials: KA
authors.lastname: Adler
authors.forename: Elaine
authors.initials: E
authors.lastname: Dillon
authors.forename: Christy J
authors.initials: CJ
authors.lastname: Perez
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mills
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D005338:Fibrin Fibrinogen Degradation Products; D014841:von Willebrand Factor; D011433:Propranolol; D007545:Isoproterenol