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3 Table 1 Dilating effects of various drugs on arteries pre-contracted with U46619 (20 nm) and comparison of IC50s Table 2 Dilating effects of various drugs on arteries pre-contracted with KCI (25 mm) and comparison of IC50s

4 Fig. 1 Concentration-response curve to sero tonin in canine basilar arteries and effect of naftidrofuryl pretreatment. Data are shown as means with S.E.M. N=5: No. of animals. One series of experiments consisted of trip licate estimations of the serotonin response, performed consecutively. Pretreatment by naftidrofuryl was performed before the second estimation. Each point is a second estimate expressed as percentage of the mean of initial and third estimates. -0: no pretreatment; 0-0: naftidrofuryl, 0.1 pm; A-A: naftidro furyl, 0.3 pm; E]-E]: naftidrofuryl, 1.0 pm. * and **: the second estimate is significantly different from the mean of initial and third estimates at the P levels of <0.05 and <0.01, respectively. Fig. 2 Concentration-response curve to sero tonin in canine femoral arteries and effect of naftidrofuryl pretreatment. Data shown as means (N=6) with S.E.M. -0: no pretreat ment; 0-0: naftidrofuryl, 0.1 pm; A-A: naftidrofuryl, 0.3 pm; E]-F-1: naftidrofuryl, 1.0 pm. For other experimental details, refer to the legend of Fig. 1. Fig. 3 Concentration-response curve to 8-OH DPAT in canine basilar arteries and effect of naftidrofuryl treatment. Data shown as means (N=3) with S.E.M. -0: no pretreatment; 0-0: naftidrofuryl, 0.3 pm; A-A: naftidro furyl, 1.0 JAM; E-0: naftidrofuryl, 3.0 pm. For other experimental details, refer to the legend of Fig. 1.

5 Fig. 4 A schematic drawing of phenylephrine-contraction of endothelium denuded carotid artery and relaxation which occurred during superfusion with the perfusate through the intact carotid artery (ca. 6 cm in length). One set of measurements consisted of control (Ai), test (B) and control (A2) runs. A % decrease of contraction was calculated as follows: for the control as the mean of two runs (Al and A2)/C x 100 and for the test, as B/Cx100. Table 3 Naftidrofuryl-induced release of vaso dilating factor from canine carotid artery into the perfusate as bioassayed on endothelium denuded and phenylephrine-precontracted artery

1) Szarvashi, E., Bayssat, M. and Fontaine, L.: C.R. Acad. Sci. Paris 260, 3095 (1965) 2) Szarvashi, E., Bayssat, M., Fontai ne, L. and Grand, (1967) M.: C.R. Acad. Sci. Paris 274, 1087 3) Szarvashi, E.

6 1) Szarvashi, E., Bayssat, M. and Fontaine, L.: C.R. Acad. Sci. Paris 260, 3095 (1965) 2) Szarvashi, E., Bayssat, M., Fontai ne, L. and Grand, (1967) M.: C.R. Acad. Sci. Paris 274, ) Szarvashi, E., Bayssat, M., Fontaine, L. and Grand, M.: Bull. Soc. Chim. France 1966, 1838 (1966) 4) Levy, L.L. and Wallace, J.D.: Stroke 8, 189 (1977) 5) Admani, A.K.: Br. Med. J. 2, 1678 (1978) 6) Clyne, C.A.C, Galland, R.B., Fox, M.J., Gustave, R., Jantet, G.H. and Jamieson, C.W.: Br. J. Surg. 67, 347 (1980) 7) Radtke, H., Kiesewetter, H., Roggenkamp, H.G. and Jung, F.: Med. Welt. 34, 833 (1983) 13) Cosnier, D., Cheucle, M., Risplat, G. and Streichenberger, G.: Arzneimittelforschung 27, 1566 (1977) 14) Luong, T.-N. and Depin, J.-C.: J. Pharmacol. (Paris) 12, 263 (1981) 15) Young, A.R., Barry, D.I., Mackenzie, E.T. and Robert, J.-P.: Eur. Neurol. 22, 142 (1983) 16) Plotkine, M., Paultre, C.Z., Boulu, R. and Rossignol, P.: Therapie 30, 713 (1975) 17) Le Poncin-Lafitte, M., Grosdemouge, C. and Roy-Billon, C.: Arch. Int. Parmacodyn. Ther. 260, 1 (1982) 18) Rosenblum, W.L.: Arzneimittelforschung 37,

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7 495 (1987) 19) Maloteaux, J.M., Hajech, J., De Campencere, D., Berta, P. and Vidal, N.: Arzneimittel forschung 36, 1195 (1986) 20) Zander, J.F., Aarhus, L.L., Katusic, Z.S., Rubanyi, G.M. and Vanhoutte, J. Pharmacol. Exp. Ther. 239, 760 (1986) 21) Furchgott, R.F.: Annu. Rev. Pharmacol. Toxicol. 24, 175 (1984) 22) Palmer, R.M.J., Rees, D.D., Ashton, D.S. and Moncada, S.: Biochem. Res. Commun. 153, 1251 (1988) 23) Rubanyi, G.M., Lorenz, R.R. and Vanhoutte, P.M.: Am. J. Physiol. 249, H95 26) Vanhoutte, P.M.: Int. J. Cardiol. 14, 189 (1987) 27) Reinhard, J.F., Liebmann, J.E., Schlosberg, A.J. and Moskowiz, M.A.: Science 206, 85 (1979) 28) Griffith, S.G., Lincoln, J. and Burnstock, G.: Brain Res. 247, 388 (1982) 29) Edvinsson, L., Degueurce, A., Mackenzie, E.T. and Scatton, B.: Nature 306, 55 (1983) 30) Holmsen, H.: In Serotonin and the Cardio vascular System, Edited by Vanhoutte, P.M., p. 75, Raven Press, New York (1985) 31) Peroutka, S.J.: Annu. Rev. Neurosci. 11, 45 (1988) 32) Muller-Schweinitzer, E. and Engel, G.: Naunyn Schmiedebergs Arch. Pharmacol. 324, 287 (1983) 33) Taylor, E.W., Duckless, S.P. and Nelson, D.L.: J. Pharmacol. Exp. Ther. 236, 118 (1986) 34) Peroutka, S.J., Huang, S. and Allen, G.S.: J. Pharmacol. Exp. Ther. 237, 901 (1986) 35) Middlemiss, D.N. and Fozard, J.R.: Eur. J. Pharmacol. 90, 151 (1983) 36) Cohen, R.A., Shepherd, J.T. and Vanhoutte, P.M.: Am. J. Physiol. 245, H1077 (1983) 37) Jackson, W.F.: Blood Vessels 25, 144 (1988) Abstract-Evaluation of the vasodilating effect of naftidrofuryl oxalate using isolated canine and rat artery preparations. Masao KOIDA*, Hiromichi NAKAMUTA*, Keiko MUGURUMA*, Hiroshi SAKURAI*, Yoshinori YOSHIHARA*, Yoshihiko ITOKAZU*, Takayuki KINOSHITA*, Yasunao OGAWA** and Yasuzo HIRAMATSU** (*Department of Pharmacology, Faculty of Pharmaceutical Sciences and **Research Institute of Drug Safety, Setsunan University, Nagaotohge-cho 45-1, Hirakata, Osaka , Japan). Folia pharmacol. japon. 94, (1989) Using isolated ring preparations of major arteries mainly of canine origin, we attempted to explore the mechanism of the vasodilating effect of naftidrofuryl oxalate (I) at the concentration of `10ƒÊM. 1) The resting tension of canine carotid, femoral, coronary, renal and basilar arteries were not affected by I. 2) A weak or no papaverine-like activity was noted on coronary, renal and basilar arteries contracted by KCl (25 mm) or U46619 (20 nm). Porcine endothelin (30 nm)-induced contraction in the basilar artery also showed no response to I. 3) I produced a relatively strong anti-serotonergic effect in the basilar and femoral arteries, and the minimum effective concentrations of I for pretreating these arteries were 0.3 and 0.1 ƒêm, respectively. I failed, however, to affect 8-OH-DPAT-induced contraction of the basilar artery. 4) In a low concentration such as 1 nm, I was able to release the vasodilating factor from the carotid artery. 5) The oscillatory contractions which developed in the rat thoracic aorta with phenylephrine (10ƒÊM) were not affected by I ( `0.1ƒÊM). 6) Na oxalate ( `1 mm) produced none of the effects of I described in 2) `4). Based on the results obtained, it is concluded that I would exert its vaso dilating effect not only directly via an anti-serotonergic action but also indirectly via its secretagogue-like action.

Study on Application of the cos a Method to Neutron Stress Measurement Toshihiko SASAKI*3 and Yukio HIROSE Department of Materials Science and Enginee

Study on Application of the cos a Method to Neutron Stress Measurement Toshihiko SASAKI*3 and Yukio HIROSE Department of Materials Science and Engineering, Kanazawa University, Kakuma-machi, Kanazawa-shi,