title: Sympathectomy decreases and adrenergic stimulation increases the release of tissue plasminogen activator (t-PA) from blood vessels: functional evidence for a neurologic regulation of plasmin production within vessel walls and other tissue matrices.
abstract: Our recent morphologic studies indicated that peripheral nervous system (PNS) adrenergic neurons synthesize, transport, and store the serene protease, tissue plasminogen activator (t-PA) in axon terminals, many of which innervate vessel walls. Sympathoadrenal stimulation induces a surge of t-PA from vessel walls into the blood. The vascular endothelium, which constitutively secretes t-PA into blood also has long been widely assumed to be the principal source of this stress-induced release, but has not been verified as such. A neurologically regulated release from adrenergic stores could thus augment the known constitutive endothelial release. To functionally test this possibility, we quantitated the effects of guanethidine-induced systemic sympathectomy on the basal and stimulated release of t-PA from isolated vessel explants in superfused organ cultures. Moment-to-moment changes in the release rate were plotted from serial assays of the t-PA free activity. The effects of endothelial and adventitial nerve plexus ablations were also tested. Sympathectomy induced 30-50% reductions in t-PA release from both arterial and microvascular explants. An acute release induced by alpha-1 adrenergic receptor stimulations was also strongly suppressed, as were basal levels of the circulating enzyme in vivo. Adventitial and endothelial ablations from normal large vessel explants produced greater reductions than small vessel endothelial ablations. Ganglion electrical stimulation also induced an acute microvascular release in vivo. These and past morphologic findings indicate a physiological infusion of t-PA into the vessel walls, blood, and other innervated matrices by sympathetic neurons.
authors.affiliation: Department of Pathology, University of Connecticut Health Center, Farmington 06030-3105, USA.
authors.forename: T
authors.initials: T
authors.lastname: Peng
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Hand
authors.forename: C
authors.initials: C
authors.lastname: Gillies
authors.forename: R E
authors.initials: RE
authors.lastname: Cone
authors.forename: J
authors.initials: J
authors.lastname: O'Rourke
mesh_terms: D000818:Animals; D001011:Aorta / Q000294:innervation / Q000502:physiology; D001808:Blood Vessels / Q000294:innervation* / Q000502:physiology*; D002339:Carotid Arteries / Q000294:innervation / Q000502:physiology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005341:Fibrinolysin / Q000096:biosynthesis*; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017783:Superior Cervical Ganglion / Q000502:physiology*; D013563:Sympathectomy, Chemical; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin