Plasmin induces endothelium-dependent nitric oxide-mediated relaxation in the porcine coronary artery.
OBJECTIVE
Plasmin is a key enzyme in fibrinolysis. We attempted to determine the possible role of plasmin in the regulation of vascular tone, while also investigating the mechanism of plasmin-induced vasorelaxation.


RESULTS
In porcine coronary artery, plasmin induced an endothelium-dependent relaxation. This relaxing effect was mostly abolished by a proteinase inhibitor, a plasmin inhibitor, or a nitric oxide (NO) synthase inhibitor. The preceding stimulation with plasmin significantly inhibited the subsequent relaxation induced by thrombin but not that induced by proteinase-activated receptor-1-activating peptide. The relaxation induced by trypsin and substance P remained unaffected by the preceding plasmin stimulation. The pretreatment with plasmin, thrombin, or trypsin significantly attenuated the plasmin-induced relaxation. In porcine coronary artery endothelial cells (PCAECs) and human umbilical vein endothelial cells (HUVECs), plasmin induced a transient elevation in the cytosolic Ca2+ concentrations ([Ca2+]i). The preceding stimulation with plasmin inhibited the subsequent [Ca2+]i elevation induced by thrombin but not that induced by trypsin. In PCAECs, plasmin concentration-dependently induced NO production.


CONCLUSIONS
The present study demonstrated, for the first time, that plasmin induced an endothelium-dependent NO-mediated relaxation in the porcine coronary artery, while also showing plasmin to specifically inactivate the thrombin receptor.
Fujiyoshi
Tetsuhiro
T
Division of Molecular Cardiology, Research Institute of Angiocardiology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Hirano
Katsuya
K
Hirano
Mayumi
M
Nishimura
Junji
J
Takahashi
Shosuke
S
Kanaide
Hideo
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D005341:Fibrinolysin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009994:Osmolar Concentration; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009569:Nitric Oxide; D014357:Trypsin; D013917:Thrombin; D005341:Fibrinolysin; D002118:Calcium