A34 Abstracts, ISHR Japaaese Section 19th Annual Meeting

5 anabu Hayashi, Haruo Hanawa, Makoto Kodama, Yoshifusa Aizwa. Division of ~rdiology, Niigate universily Graduate School. Mikio

Nakazawa. Niigata University School of Weaith Science

retory leukocyte protease inhibiior (SLPI) is a unique protein, which inhibits serine proteases and has antimicrobial effects. Some reports

have shown that serine protease inhi~~o~ improved several cardiovascular diseases (CVD), but effects of SLPI for myocardiis remain unclear. We investi effects on experimental autoimmune myocardiis (EAM). Lewis rats were immunized

with porcine cardiac myosin on day 0 and divided into SLPI group (treated with plasmid encoding SLPIIIgGlFc chimera) end Control group (treated with empty plasmid). Each plasmid was injected into muscule with el~tro~ra~~ and tail vein rapidly. The ratio of heart to body weight (HW~W)~ histopa~olo~, and hem~amic parameters were evaluated resp~ely at acute phase (AP) on day 17 and at chronic phase (CP) on day 40 after immunization ~~~~~ HW~W in SLPI group was sign~~~~ lower than in Controi group at either

phase. Maximum dp/dt in SLPI group at CP and Minimum dp/dt in

SLPI group at AP and at CP improved signers, The area of rny~~ia~ necrosis, itiammatoy ceil infi~at~on and fibrosis was reduced signers by SLPI. crusade SLPI reduces myocardial

sis and fibrosis by infi~mation and protects cardiac function on

Yasuyuki Watanabe, Yukio ~a~yama. F~k~sh~rna Medical

~~ivers~t~

Heme oxygenase-1 (HO-l) is induced by a variety of conditions, which induce oxidative stress in cells. Examined whether this HO-1 expression influences reactive oxygen species (ROSI productions and pro-~romboti~ processes. ~mb~onic ~broblas~ (El 1.5) from HO-1 deficient mice were prepared, cui~~d and exposed to oxidized LDL. The expression level of ~iesm~nogen ac~vator inh~b~to~l (PAI- and ROS produc~ons En HO-1 deficient cells were compa~d to those from wild-type mice by western blot analysis and dichiorodihyd~fluorescein d&et&e assay. Complemental effects of biii~bi~ (BR: a reaction product of HO), ~u~ione (GSH). desfe~oxamine (DFO). di~henyle~e-~odoflium (DPI: a NADPH oxidase ~h~bitor) on PAI- expression and ROS production were examined. PM-1 expression and ROS produc~on were markedly elevated in HO-1 de~cie~~ cells compared to wil~ype at stable state condition. PAS-1 expression and ROS production a LDL exposures were further eleva~d in both cells, however. si~~c~~y higher in HO-1 deficient cells. Interes~fl~y, the alevetions of PAI- end ROS p~ductions in HO-1 deficient cells were si~‘~ca~~~ lowered by the prevalent with BR and GSH, and partly with DFO while DPI p~~ea~ent had little

cts. Cellular HO-1 deficiency may lead to the increase in OS p~~ctions followed by PM-1 induction. These results

suggest the possibi~~ies at HO-1 may function against rombus fo~atio~ through antioxid~t bili~bin production and e effect on cellular redox state such as ~lu~~ione system.

P-38 ED

Yasufusa Ohgai, Takashi oikawa, Naomi Yagi, Akira Sekikawa, Yukiko Tokumitsu, Tatsuya Nayai’, Koichi ala’, Kazuya Yonezawa’, Hirotaka Nishiiima . Tsutomu Honiou? Noriteru Motita’, Ker$ lizuka’, Take&hi k&akarni’, Akira Kliiabatake’, Hideaki Kawaauchi’. He&h 5%. Univ. Hokkaido. ’ HoW<aido Univ. Graduat; Sch.‘&&., ‘Sappotu Health Promotion Center, 3Morinaga Inst. Biol. Sci. Yokohama, Japan.

F D~SSOC~TI ILITY OF L §-XT2 ~TA~~NISTS IN MUSCARI-

EART M~unur Rashid, Mikio Nakazawal and Takatitni

Nagatomo. Dept of Pharmacology, Niigata College of Pharmacy, Niigata, Japan; ‘Dept of Medical Technology, Faculty of Medicine, Niigata University, Niigata, Japan.

In our previous study, we observed that sarpogrelate and ketanserin were rapidly dissociated from 5-HTz receptors in rabbit cerebral cortex membrane. The blockade of [3H]ket~serin binding sites in the rabbit cerebral cortex induced by ketanserin and sarpogrelate was readily reversed by washing, whereas the inhibition by c~ro~eptadine and ritanserin was not readily reversed by was~ng using the method of centrifugation, resuspension and radiolig~d binding assay. The aim of the present study is to investigate the binding affinity and dissociation ability of several 5-HTz antagonisrs in muscarinic receptor of rat heart using [3H]Q~ as a radioligand. The result showed that sarpogrelate and ketanserin had very weak affinity to muscarinic receptor, whereas cyproheptadine had high binding affinity to this receptor. However all these three 5-HT2 antagonists were readily dissociated from muscarinic receptor in rat heart after washing. The investigation suggests that the interaction sites of these 5- HT2 antagonists to 5-HT2 receptor may be different from that of muscarinic receptor and sarpogrelate has less side effects in respect with its clinical implication.