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Fig. 1 Excised canine lung lobe preparation. The lobe was perfused with the pulsatile pump (Harvard 1405) and ventilated with a positive respirator.

2 Fig. 1 Excised canine lung lobe preparation. The lobe was perfused with the pulsatile pump (Harvard 1405) and ventilated with a positive respirator. P1, F1: pressure and flow pattern just after pulsatile pump, P2i F2: pressure and flow pattern at the inflow site of the lobe, P3i F3: pressure and flow pattern at the outflow site of the lobe

3 Fig. 2 Effects of serotonin, noradrenaline, prostaglandin F2a and histamine on the pressures and flows in the excised canine lung lobe preparation. Each of the agents elevated inflow pressure (P2) to the same degree in both antegrade and retrograde perfusion. But serotonin and noradrenaline markedly decreased the flow amplitude at the inflow site of the lobe (F2) in the antegrade perfusion, while prostaglandin F2a and histamine did in the retrograde perfusion. Table 1 Changes in % dr and % JFA2 after serotonin injection

4 Antegrade Perfusion Retrograde Perfusion Fig. 3 Changes in %AR and %dfa2 after serotonin, noradrenaline, prostaglandin F2a and histamine injection at each maximal dose. Each of the agents increased %4R to the same degree in both antegrade and retrograde perfusion. Serotonin and noradrenaline markedly decreased %dfa2 in the antegrade perfusion, but did not in the retrograde perfusion. On the contrary, prostaglandin F2a and histamine markedly decreased %dfa2 in the retrograde perfusion, but did not in the antegrade perfusion. 5HT: 100pg(a), NA: 100, ug(o), PGF2a: 30, ug(), Hist.: l0yg (A).

5 Table 2 Changes in %dr and %dfa2 after noradrenaline injection Antegrade Perfusion (n.1g) Retrograde P(=m16) Fig. 5 Correlation between %dr and %dfa2 after noradrenaline injection. Noradrenaline decreased %dfa2 more markedly in the antegrade perfusion than in the retrograde perfusion predominantly (p=n.s.). antegrade perfusion: y= x, y= , p<0.01, retrograde perfusion: y= x, y= , p <0.01

6 Table 3 Changes in %dr and %JFA2 after prostaglandin F2a injection

7 Table 4 Changes in %dr and %dfa2 after histamine injection Retrograde Perfusion (n16) Antegrade Perfusion (n=16) Fig. 7 Correlation between %dr and %dfa2 after histamine injection. Histamine decreased % dfa2 more markedly in the retrograde perfusion than in the antegrade perfusion significantly (p< 0.05). antegrade perfusion: y= x, y= , p<0.05, retrograde perfusion: y= x, y= , p<0.01

2) Said, S.I.: The lung in relation to vasoactive hormones. Fed. Proc., 32: 1972, 1973. 3) Friedman, W.F. & Braunwald, E.

9 2) Said, S.I.: The lung in relation to vasoactive hormones. Fed. Proc., 32: 1972, ) Friedman, W.F. & Braunwald, E.: Alterations in regional pulmonary blood flow in mitral valve disease studied by radioisotope scanning. A simple nontraumatic technique for estimation of left atrial pressure. Circulation, 34: 363, ) Grover, R.F., Wagner, W.W.Jr., McMurtry, I. F. & Reeves, J.T.: Pulmonary circulation. In Handbook of Physiology, edited by Shepderd, J. T. & Abboud, F.M., Williams & Wilkins, Baltimore, 1983, p ) Joiner, P.D., Kadowitz, P.J., Davis, LB. & Hyman, A.L.: Contractile responses of canine isolated pulmonary lobar arteries and veins to norepinephrine, serotonin, and tyramine. Can.J. Physiol. Pharmacol., 53: 830, ) Gilbert, R.P., Hinshaw, LB., Kuida, H. & Visscher, M. B.: Effects of histamine, 5- hydrotryptamine and epinephrine on pulmonary hemodynamics with particular reference to arterial and venous segment resistance. Am. J. Physiol., 194: 165, ) Glazier, J.B. & Murray, J.F.: Sites of pulmonary vasomotor reactivity in the dog during alveolar hypoxia and serotonin and histamine infusion. J. Clin. Invest., 50: 2550, ) Hyman, A.L.: The direct effects of vasoactive agents on pulmonary veins. Studies of responses to acetylcholine, serotonin, histamine and isoproterenol in intact dog. J. Pharmacol. Exp. Ther., 168: 96, ) Dawson, C. A., Rickaby, D.A. & Linehan, J. H.: Pulmonary capillary pressure in the dog lung as determined by lobar arterial and venous occlusion. Fed. Proc., 40: 503, ) Hakim, T. S., Dawson, C.A. & Linehan, J.H.: Hemodynamic responses of dog lung lobe to lobar venous occlusion. J. Appl. Physiol., 47: 145, ) Linehan, J. H. & Dawson, C. A.: Distribution of pulmonary vascular resistance (R) and compliance (C) in the dog lung lobe as determined by vascular occlusion. Fed. Proc., 40: 503, ) Sackner, M. A., Will, D. H. & DuBois, A. B.: The site of pulmonary vasomotor activity during hypoxia or serotonin administration. J. Clin. Invest., 45: 112, ) Hyman, AL.: The direct effects of noradrenaline and of angiotensin on the pulmonary veins of intact dogs. J. Pharmacol. Exp. Ther., 165: 87, ) Feeley, J.W., Lee, T.D. & Milnor, W. R.: Active and passive components of pulmonary vascular response to vasoactive drugs in the dogs. Am. J. Physiol., 205: 1193, ) Nakano, J. & McCurdy, J. R.: Hemodynamic effects of prostaglandins E1, Al and F2a in dogs. Proc. Soc. Exp. Biol. Med., 128: 39, ) Ducharme, D. W., Weeks, JR. & Montgomery, R. G.: Studies on the mechanism of the hypertensive effect of prostaglandin macol. Exp. Ther., 160: 1,1968. F2a. J. Phar-

10 Abstract The Site of Action of Vasoactive Agents on the Pulmonary Vascular Bed in Excised Canine Lung Lobe Preparations Perfused with Pulsatile Flow Takashi Haneda, Hirohisa Yamashita and Katsuyuki Tobise The First Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan It is very difficult to study the proper effects of vasoactive agents on the pulmonary vascular bed in vivo, because hemodynamic changes in the pulmonary circulation will be markedly influenced by changes in the systemic circulation induced by the treatment with these agents. Therefore we used the excised canine lung lobe perfused through the pulmonary artery (antegrade perfusion) with pulsatile flow to study the response of the pulmonary vascular bed to vasoactive agents, and reported that serotonin markedly decreases flow amplitude (amplitude of the flow wave produced by pulsatile perfusion) at the inflow site of the lobe following pulmonary vascular constriction, whereas histamine that also has a constrictive action does not affect flow amplitude. This fact indicates that serotonin and histamine act on the pulmonary vascular bed in different manners. The present study was undertaken to determine the main site of action of the agents and to explain the reason why the effects of vasoconstrictive agents on flow amplitude are different. The excised lung lobe was perfused either via the pulmonary artery (antegrade perfusion) or pulmonary vein (retrograde perfusion) with pulsatile flow. Changes in flow amplitude at the inflow site of the lobe due to the treatment with vasoactive agents (serotonin, noradrenaline, prostaglandin F2 and histamine) were observed in both preparations perfused with antegrade and retrograde flow. Each of the agents elevated lobe inflow pressure to the same degree in both antegrade and retrograde perfusion, indicating that pulmonary vasoconstriction occurred. Regarding flow pattern, serotonin and noradrenaline markedly decreased flow amplitude in the antegrade perfusion, while prostaglandin retrograde F2 and histamine decreased it in the perfusion. Since we have shown in a previous paper that a decrease in the flow amplitude reflects a decrease in compliance due to constriction of the proximal vessels in the lung lobe, it is very rational to consider that serotonin and noradrenaline mainly constrict the arterial side of the pulmonary vascular bed, and prostaglandin F2 and histamine mainly constrict the venous side. In conclusion, this experiment suggested that the predominant site of the action of serotonin and noradrenaline is the arterial side of the pulmonary vascular bed, and that of prostaglandin FED and histamine is the venous side.

Experimental and Clinical Studies of Pregnant Hypertension Takashi SHIMAZU Department of Obstetrics and Gynecology, Osaka City University Medical Scho

Experimental and Clinical Studies of Pregnant Hypertension Takashi SHIMAZU Department of Obstetrics and Gynecology, Osaka City University Medical School While the problem of late pregnant hypertension