Protective effects of human urinary trypsin inhibitor against trypsin-induced relaxation in rat aorta.
OBJECTIVE
To investigate the vasodilatory responses induced by trypsin, and to determine the antitrypsin effects of human urinary trypsin inhibitor on blood vessels.


METHODS
Prospective, randomized, controlled study, with repeated measurements.


METHODS
University research laboratory.


METHODS
The isometric tension of the aortic rings isolated from male Wistar rats was recorded. The vasodilatory responses to varying amounts of trypsin (0.01 to 10 U/mL) were examined under pretreatment with human urinary trypsin inhibitor (1 to 10 U/mL), chicken-egg-white trypsin inhibitor (0.1 to 10 mg/mL), N infinity-nitro-L-arginine (3 x 10(-5) M), and denudation of the endothelium. In addition, with the scanning electron microscopy, the endothelium of aorta was examined under treatment with trypsin alone (10 U/mL), and with trypsin plus human urinary trypsin inhibitor (10 U/mL each).4


RESULTS
The addition of trypsin produced dose-dependent relaxation in aortic rings with an intact endothelium, which was abolished by denudation and treatment with N infinity-Nitro-L-arginine. Pretreatment with human urinary trypsin inhibitor and with chicken-egg-white trypsin inhibitor caused dose-dependent inhibition against trypsin-induced vasorelaxation. On the repeated trials of the response to trypsin, the responses gradually developed tachyphylaxis in control aortic rings, whereas no tachyphylaxis developed in rings pretreated with human urinary trypsin inhibitor (10 U/mL). Scanning electron microscopy demonstrated endothelial disruption in aorta exposed to trypsin alone, whereas the endothelium was intact in strips treated with trypsin plus human urinary trypsin inhibitor.


CONCLUSIONS
The data indicate that relaxation induced by trypsin is attributable to nitric oxide released from the endothelium, and that human urinary trypsin inhibitor protects vessels against trypsin-induced endothelial injury. It appears that the clinical antishock effect of human urinary trypsin inhibitor is ascribable in part to its antitrypsin activity on the endothelium of vascular smooth muscle.
Department of Anesthesiology, Wakayama Medical College, Japan.
T
T
Ooka
Y
Y
Hatano
M
M
Yamamoto
K
K
Ogawa
S
S
Saika
D000818:Animals; D001011:Aorta / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D014361:Trypsin Inhibitors; D014357:Trypsin