Stimulated release of tissue plasminogen activator from artery wall sympathetic nerves: implications for stress-associated wall damage.
Recurrent stress is clinically associated with early onset hypertension and coronary artery disease. A mechanism linking emotion to pathogenic remodeling of the artery wall has not been identified. Stress stimulates acute regulated release of tissue plasminogen activator (t-PA) into the circulation, which is presently attributed to the vascular endothelium. Sympathetic neurons also synthesize t-PA and axonally transport it to the arterial smooth muscle. Unlike release by the endothelium, a stress-stimulated sympathetic discharge would potentially accelerate degradation of the wall matrix by plasmin. To assess whether sympathetic axons are the principal source of acute stress-induced arterial release of t-PA, we compared the output from small densely innervated and large sparsely innervated isolated artery segments before and after sympathetic stimulation, and after ablations. Following phenylephrine infusion densely-innervated microvessels in uveal eyecups were released over 60-fold greater amounts of active t-PA per milligram than the sparsely innervated aorta; and ten-fold more than carotid artery segments. Mesenteric artery release was 4.8-fold greater than release by the carotid artery. In vivo, uveal release of t-PA increased more than three-fold within one minute following superior cervical sympathetic ganglion electrical stimulation, and after phenylephrine, or nicotine infusions of the anterior chamber. Circulating levels of t-PA fell 70% following chemical sympathectomy. We propose that sympathetic nerves are the primary source of stress-induced release of t-PA into and from the densely innervated resistance arteries and arterioles, where dysregulated plasmin-induced proteolysis could damage the wall matrix.
Hao
Zhifang
Z
Department of Pathology, University of Connecticut Health Center, Farmington 06030-3105, USA.
Jiang
Xi
X
Sharafeih
Roshanak
R
Shen
Shujing
S
Hand
Arthur R
AR
Cone
Robert E
RE
O'Rourke
James
J
D000818:Animals; D003327:Coronary Disease / Q000523:psychology; D004195:Disease Models, Animal; D005260:Female; D006973:Hypertension / Q000523:psychology; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000201:enzymology / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology; D008833:Microcirculation / Q000294:innervation / Q000502:physiology / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000294:innervation / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D010959:Tissue Plasminogen Activator