URINARY TRYPSIN-INHIBITOR SUPPRESSES VASCULAR SMOOTH-MUSCLE CONTRACTION BY INHIBITION OF CA2+ INFLUX

Urinary trypsin inhibitor (UTI) and its precursor form inter-alpha try psin inhibitor (ITI) are present in plasma. To determine the action of UTI on blood vessels, we performed isometric vascular muscle contract ion tests, microcirculation studies and measurement of cytosolic free Ca2+ in vascular smooth muscle cells. An isometric vascular muscle con traction test showed that the contractions stimulated by endothelin-1 or norepinephrine were suppressed in the presence of UTI, and that the contractions were not inhibited in the presence of ITI. The microcirc ulation study showed that the contraction of mesenteric arterioles of WKY rats induced by norepinephrine were inhibited by treatment of UTI, and that they did not alter by treatment of ITI. Pre-incubation of UT I, but not ITI, with vascular smooth muscle cells inhibited the increa se of cytosolic free Ca2+ induced by endothelin-1 or norepinephrine. C ell-binding study by biotinylated UTI showed that vascular smooth musc le cells have specific binding site for UTI, but not for ITI. We propo se that circulating UTI converted from ITI has a regulatory effect on local vascular tone by regulation of Ca2+ influx into smooth muscle ce lls. (C) 1998 Elsevier Science B,V. All rights reserved.