Sen Cui

Kanazawa Medical University, Kanazawa-shi, Ishikawa-ken, Japan

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Publications (23)56.76 Total impact

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    ABSTRACT: Summary1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the venoconstriction of perfused livers was also examined.2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (Ppv) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (Rpre and Rpost, respectively). In conscious rats, systemic arterial pressure (SAP) and Ppv were determined.3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in Rpre and Rpost, respectively. The anaphylaxis-induced increase in Rpre was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with NG-nitro-l-arginine methyl ester (100 ╬╝mol/L) 10 min prior to the injection of antigen enhanced anaphylactic venoconstriction, but did not alter the effect of exercise training on the increase in Rpre. In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats.4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in conscious rats.
    Clinical and Experimental Pharmacology and Physiology 08/2010; 37(9):889 - 893. · 2.41 Impact Factor
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    ABSTRACT: We previously reported that the portal venous pressure (PPV) response of perfused mouse livers to various vasoactive agents was much weaker than that of other mammals such as rat, rabbit, and guinea pigs. The purpose of this study was to determine the responsiveness of PPV in in vivo BALB/c mouse to intraportal injections of the 3 major vasoconstrictors of angiotensin II, norepinephrine, and endothelin-1 in comparison with that in Sprague-Dawley rats. In anesthetized spontaneously breathing animals, PPV, systemic arterial pressure, and central venous pressure were directly and continuously measured. The above-mentioned vasoconstrictors were injected into the portal vein as a bolus repetitively at the doses ranging 0.01-100 nmol/kg. A dose-dependent increase in systemic arterial pressure in response to each vasoconstrictor was observed similarly in both mice and rats. All vasoconstrictors also caused a dose-dependent increase in PPV in both species, but the peak levels in mouse did not reach higher than 7 mm Hg, whereas it reached as high as 15-24 mm Hg in rats. Immunostaining for alpha-smooth muscle actin revealed that smooth muscles were distributed substantially in portal venules of rat but scarcely in that of mouse. In conclusion, PPV response to various vasoconstrictors was limited in anesthetized BALB/c mice, as compared with the anesthetized Sprague-Dawley rats, presumably due to small amount of vascular smooth muscle in mouse portal venules.
    Journal of cardiovascular pharmacology 11/2009; 54(5):421-6. · 2.83 Impact Factor
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    ABSTRACT: We determined the roles of platelet-activating factor (PAF) and histamine in anaphylactic hypotension in ovalbumin-sensitized anesthetized BALB/c mice. The effects of PAF and histamine on hemodynamic variables were studied by measuring the systemic arterial (Psa), portal venous (Ppv) and central venous (Pcv) pressures. Intravenous PAF evoked a biphasic Psa response, an initial rapid and transient drop followed by marked hypotension, accompanied by a decrease in Pcv. Histamine caused only mild systemic hypotension. Both agents similarly increased Ppv by approximately 4 cm H(2)O at high doses. After an injection of antigen, Psa initially increased slightly and then decreased from the baseline of 94 +/- 1 mm Hg to 46 +/- 1 mm Hg at 10 min after antigen administration, with Pcv decreasing by 2.5 cm H(2)O. Ppv increased by 3.5 cm H(2)O at 5 min after antigen injection. Pretreatment with either CV-6209 (PAF receptor antagonist, 1 mg/kg) or diphenhydramine (histamine H(1) receptor antagonist, 20 mg/kg) significantly attenuated an antigen-induced decrease in Psa. The inhibitory action of CV-6209 was greater than that of diphenhydramine, and the combination of these 2 antagonists almost completely inhibited the anaphylactic hypotension. In contrast, the antigen-induced increase in Ppv was attenuated by CV-6209 alone but augmented by diphenhydramine. It is concluded that anaphylactic hypotension is mainly mediated by PAF and, to a lesser extent, by histamine in anesthetized BALB/c mice.
    Pharmacology 07/2008; 82(2):114-20. · 1.60 Impact Factor
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    ABSTRACT: The roles of NO and isozymes of NO synthase (NOS) are not known in anaphylactic hypotension of unanesthetized rats. Effects of inhibition of NOS, iNOS, and nNOS by N-nitro-L-arginine methyl ester (L-NAME), aminoguanidine, and 7-nitroindazole, respectively, were determined on the antigen-induced systemic hypotension and portal hypertension in conscious Sprague-Dawley rats sensitized with the ovalbumin antigen. The MAP and portal venous pressure were directly and simultaneously measured. The control rats showed a decrease in MAP along with an increase in portal venous pressure but did not die within 48 h after antigen injection. In the rats pretreated with the nonselective NOS inhibitor L-NAME (10 mg/kg), MAP before and after antigen administration was significantly higher than that of the control rats, but the net decrease in MAP and increase in portal venous pressure were rather greater than those of the control, resulting in fatal outcome within 12 h after antigen administration. In contrast, pretreatment with the relatively selective nNOS inhibitor 7-nitroindazole (50 mg/kg) substantially attenuated anaphylactic hypotension over 20 min after antigen administration, whereas the relatively selective iNOS inhibitor aminoguanidine (100 mg/kg) did not affect it. In conclusion, in anaphylactic hypotension of unanesthetized rats, NO derived from nNOS, but not from iNOS, may be involved, and the nonselective NOS inhibitor L-NAME is lethal.
    Shock (Augusta, Ga.) 06/2008; 31(2):201-6. · 2.87 Impact Factor
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    ABSTRACT: Mast cells and other cells such as macrophages have been shown to mediate systemic anaphylaxis. We determined the roles of mast cells and Kupffer cells in hepatic and systemic anaphylaxis of rats. Roles of mast cells were examined by using the mast cell-deficient white spotting (Ws/Ws) rat; the Ws/Ws and wild type (+/+) rats were sensitized with ovalbumin (1 mg). Roles of Kupffer cells were examined by depleting Kupffer cells using gadolinium chloride or liposome-encapsulated dichloromethylene diphosphonate in the Ws/Ws and Sprague-Dawley rats. An intravenous injection of 0.6 mg ovalbumin caused substantial anaphylactic hypotension in both the Ws/Ws and +/+ rats; however, the occurrence was delayed in the Ws/Ws rats. After antigen, portal venous pressure increased by 13.1 cmH2O in the +/+ rats, while it increased only by 5.7 cmH2O in the Ws/Ws rats. In response to antigen, the isolated perfused liver of the Ws/Ws rats also showed weak venoconstriction, the magnitude of which was one tenth as large as that of the +/+ rats, indicating that hepatic anaphylaxis was primarily due to mast cells. In contrast, Kupffer cell depletion did not attenuate anaphylactic hepatic venoconstriction in isolated perfused livers. In conclusion, mast cells are involved mainly in anaphylactic hepatic presinusoidal portal venoconstriction but only in the early stage of anaphylactic systemic hypotension in rats. Macrophages, including Kupffer cells, do not participate in rat hepatic anaphylactic venoconstriction.
    AJP Regulatory Integrative and Comparative Physiology 01/2008; 293(6):R2202-9. · 3.28 Impact Factor
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    ABSTRACT: Hepatic anaphylactic venoconstriction is partly involved in anaphylactic hypotension. We determined the chemical mediators responsible for anaphylaxis-induced segmental venoconstriction in perfused livers isolated from ovalbumin-sensitized rats. Livers were perfused portally and recirculatingly at constant flow with diluted blood. The portal venous pressure (Ppv), hepatic venous pressure (Phv), liver weight and hepatic oxygen consumption were continuously measured. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost) resistances. After antigen injection, both Ppv and Pdo increased, resulting in 5.6- and 1.6-fold increases in Rpre and Rpost, respectively. Liver weight showed a biphasic change of an initial decrease followed by an increase. Hepatic oxygen consumption significantly decreased after antigen. Anaphylaxis-induced increase in Rpre was most extensively inhibited by 38.6% by pretreatment with ONO-1078 (100 microM, a cysteinyl leukotriene receptor-1 antagonist), among all antagonists or inhibitors administrated individually including TCV-309 (20 microM), AA-2414 (10 microM), ketanserin (10 microM) and indomethacin (10 microM). Combined pretreatment with indomethacin and ONO-1078 exerted additive inhibitory effects and attenuated Rpre by 65.8%. However, TCV-309, a platelet activating factor (PAF) receptor antagonist, did not affect the anaphylactic response. In contrast, anaphylaxis-induced increase in Rpost was attenuated only by ONO-1078 combined pretreatment. The antigen-induced changes in liver weight and hepatic oxygen consumption were attenuated significantly when hepatic venoconstriction was attenuated. It is concluded that cysteinyl leukotrienes and cyclooxygenase products, but not PAF, are mainly involved in anaphylaxis-induced pre-sinusoidal constriction in isolated perfused rat livers.
    European Journal of Pharmacology 01/2008; 576(1-3):99-106. · 2.59 Impact Factor
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    ABSTRACT: Using in vivo and isolated perfused liver preparations of BALB/c mice, we determined the roles of the liver and splanchnic vascular bed in anaphylactic hypotension. Intravenous injection of ovalbumin antigen into intact-sensitized mice decreased systemic arterial pressure (P(sa)) from 92 +/- 2 to 39 +/- 3 (SE) mmHg but only slightly increased portal venous pressure (P(pv)) from 6.4 +/- 0.1 cmH(2)O to the peak of 9.9 +/- 0.5 cmH(2)O at 3.5 min after antigen. Elimination of the splanchnic vascular beds by ligation of the celiac and mesenteric arteries, combined with total hepatectomy, attenuated anaphylactic hypotension. Ligation of these arteries alone, but not partial hepatectomy (70%), similarly attenuated anaphylactic hypotension. In contrast, isolated sensitized mouse liver perfused portally at constant flow did not show anaphylactic venoconstriction but, rather, substantial constriction in response to the anaphylaxis-associated platelet-activating factor, indicating that venoconstriction in mice in vivo may be induced by mediators released from extrahepatic tissues. These results suggest that splanchnic vascular beds are involved in BALB/c mouse anaphylactic hypotension. They presumably act as sources of chemical mediators to cause the anaphylaxis-induced portal hypertension, which induced splanchnic congestion, resulting in a decrease in circulating blood volume and, thus, systemic arterial hypotension. Mouse hepatic anaphylactic venoconstriction may be induced by factors outside the liver, but not by anaphylactic reaction within the liver.
    AJP Regulatory Integrative and Comparative Physiology 12/2007; 293(5):R1947-53. · 3.28 Impact Factor
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    ABSTRACT: Anaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. The increased venous resistance accounts for the anaphylactic hypotension in anesthetized dogs. However, the change in peripheral vascular resistances during anaphylactic hypotension in other animals such as rats is not known. We measured the mean circulatory filling pressure using the mechanical occlusion method of inflation of the right atrial balloon along with systemic arterial pressure (Psa), central venous pressure, and portal venous pressure. Cardiac output was also measured with the thermodilution method. From these hemodynamic variables, we calculated the total peripheral and venous (Rv) resistances during anaphylactic hypotension in anesthetized rats. These hemodynamic variables were compared with those in the hemorrhagic shock. After an intravenous injection of 0.6 mg antigen ovalbumin in sensitized rats, Psa decreased from 119 +/- 4 to 43 +/- 2 mmHg, cardiac output decreased from 84.5 +/- 5.7 to 37.8 +/- 2.1 mL min, central venous pressure decreased from 0.9 +/- 0.1 to 0.1 +/- 0.1 mmHg, and mean circulatory filling pressure also decreased from 6.0 +/- 0.2 to 5.2 +/- 0.3 mmHg. Thus, the Rv increased from 0.06 +/- 0.05 to 0.15 +/- 0.02 mmHg mL(-1) min(-1), but total peripheral resistance did not significantly change. Portal venous pressure also increased from 5.6 +/- 0.5 to 21.5 +/- 0.9 mmHg. Hematocrit markedly increased from the baseline values of 43% +/- 1% to 55% +/- 1% at 15 min after antigen. During hemorrhagic shock, Psa decreased in the manner similar to anaphylactic shock; however, Rv did not significantly change, and portal venous pressure decreased. In conclusion, in rat anaphylactic shock, a substantial increase in Rv presumably due to hepatic venoconstriction may decrease venous return, resulting in systemic hypotension.
    Shock 12/2007; 29(6):733-9. · 2.61 Impact Factor
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    ABSTRACT: Effects of L-NAME on U-46619 (a thromboxane A(2), analogue) -induced hepatic segmental venoconstriction were examined in mouse, rat and guinea pig isolated perfused livers. All livers were perfused portally and recirculatingly at a constant flow with diluted blood. U-46619 was administrated into the reservoir in a cumulative manner to gain the concentrations of 0.001-3 microM at 10 min after L-NAME or D-NAME (100 microM). The portal venous pressure, hepatic venous pressure and perfusate flow were monitored. In addition, the sinusoidal pressure was measured by the double occlusion pressure, and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. U-46619 concentration-dependently caused predominant presinusoidal constriction in all three species. The rat livers were the strongest while the mouse livers were the weakest in responsiveness and sensitivity to U-46619. L-NAME mainly augmented the U-46619-induced increases in Rpre, but not in Rpost, in rat and guinea pig. This augmentation was stronger in rat. However, L-NAME did not augment the response to U-46619 in mouse. In conclusion, in rat and guinea pig, NO may be released selectively from the presinusoids in response to U-46619, and then attenuate the U-46619-induced presinusoidal constriction. In mouse, U-46619-induced venoconstriction is weak and not modulated by NO.
    Vascular Pharmacology 11/2007; 47(4):215-21. · 3.21 Impact Factor
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    ABSTRACT: A head-down tilt posture, the Trendelenburg position, which could facilitate venous return from the splanchnic organs and lower extremities, is recommended for the treatment of anaphylactic shock. However, few data of animal studies support its effectiveness. We examined the effects of a head-down tilt maneuver on anaphylactic hypotension in BALB/c mice and Sprague-Dawley rats. We measured systemic arterial pressure (Sap) and portal venous pressure (Pvp) in spontaneously breathing anesthetized animals sensitized with ovalbumin. At either supine (control) or a 30-degree head-down tilt position, anaphylactic hypotension was induced by an intravenous injection of antigen. In the control rats, an increase in Sap by 66 mmHg and a decrease in Pvp by 11.5 cmH(2)O were observed at 2.5 and 6 min, respectively, after antigen. In contrast, in control mice injected with antigen, Sap decreased similarly, but Pvp increased by only 4 cmH(2)O. A head-down tilt maneuver in mice substantially attenuated the antigen-induced decrease in Sap throughout the 60 min measurements, though it aggravated slightly, but significantly, only at the late phase of after 25 min in rats. We conclude that a head-down tilt maneuver attenuates anaphylactic hypotension in anesthetized mice and rats. These beneficial effects were smaller in rats than in mice probably because of substantial portal hypertension, which might prevent the head-down tilt-induced increase in venous return from the splanchnic vascular bed.
    The Journal of Physiological Sciences 11/2007; 57(5):269-74. · 1.09 Impact Factor
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    ABSTRACT: To clarify the role of NO in mouse anaphylactic hypotension, effects of a nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on antigen-induced hypotension and portal hypertension were determined in anesthetized BALB/c mice. Systemic arterial pressure (Psa), central venous pressure (Pcv), and portal venous pressure (Ppv) were directly and simultaneously measured. Mice were first sensitized with ovalbumin, and then the injection of antigen was used to decrease Psa and increase Ppv. Pretreatment with L-NAME (1 mg/kg) attenuated this antigen-induced systemic hypotension, but not the increase in Ppv. The effect of inhibitors of soluble guanylate cyclase on anaphylactic hypotension were studied with either methylene blue (3.0 mg/kg) or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (10 mg/kg). Neither modulated any antigen-induced changes. Furthermore, methylene blue did not improve systemic hypotension induced by Compound 48/80 (4.5 mg/kg), a mast cell degranulator, which can produce non-immunological anaphylactoid reactions. These data show in anesthetized BALB/c mice that L-NAME attenuated anaphylactic hypotension without affecting portal hypertension. This beneficial effect of L-NAME appears not to depend on the soluble guanylate cyclase pathway.
    Journal of Pharmacological Sciences 08/2007; 104(3):212-7. · 2.15 Impact Factor
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    ABSTRACT: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation possibly caused by an increase in the sinusoidal pressure, a determinant of hepatic transvascular fluid movement. However, changes in the sinusoidal pressure during hepatic I/R in mice are not known. It is also controversial whether nitric oxide (NO) exerts a beneficial or detrimental effect on hepatic I/R injury. We determined the changes in hepatic sinusoidal pressure and liver weight, and the effect of a NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on I/R injury of isolated mouse liver. Isolated liver from 20 male outbred ddY mice was perfused portally with diluted blood (Hct 3%). After pretreatment with L-NAME (100 microm) or D-NAME (100 microm), ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h followed by 1-h reperfusion in a recirculating manner. The sinusoidal pressure was assessed by the double vascular occlusion pressure (Pdo), and pre- and postsinusoidal resistance was determined. Liver injury was assessed by blood levels of alanine aminotransferase (ALT). In the d-NAME group (n=7), immediately after reperfusion, the portal pressure increased by 2.8 +/- 0.1 (SE) mmHg, which was accompanied by an increase in Pdo of 1.5 +/- 0.1 mmHg, indicating increases in pre- and postsinusoidal resistance to a similar degree. Then, presinusoidal, but not postsinusoidal, resistance sustained increased until 60 min after reperfusion. Liver weight increased to 0.14 +/- 0.04 g/g liver after reperfusion, followed by a gradual return to baseline. Blood ALT levels increased at 60 min after reperfusion. There were no significant differences in changes in the variables between the D- and L-NAME (n=7) groups. In the time-matched non- I/R control group (n=6), no changes in variables were observed for 2 h. Mouse hepatic I/R causes marginal liver weight gain associated with a small and transient increase in the sinusoidal pressure, and nitric oxide does not play any significant roles in this injury.
    Journal of Surgical Research 06/2007; 139(1):30-5. · 2.02 Impact Factor
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    ABSTRACT: Platelet-activating factor (PAF), one of vasoconstrictive lipid mediators, is involved in systemic anaphylaxis. On the other hand, nitric oxide (NO) is known to attenuate anaphylactic venoconstriction of the pre-sinusoids in isolated guinea pig and rat livers. However, it is not known whether NO attenuates PAF-induced hepatic venoconstriction. We therefore determined the effects of L-NAME, a NO synthase inhibitor, on PAF-induced venoconstriction in blood- and constant flow-perfused isolated livers of mice, rats and guinea pigs. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. PAF (0.01-1 microM) concentration-dependently caused predominant pre-sinusoidal constriction in all livers of three species studied. The guinea pig livers were the most sensitive to PAF, while the mouse livers were the weakest in responsiveness. L-NAME pretreatment selectively increased the basal Rpre in all of three species. L-NAME also significantly augmented the PAF-induced increases in Rpre, but not in Rpost, in rat and guinea pig livers. This augmentation was stronger in rat livers than in guinea pig livers at the high concentration of 0.1 microM PAF. However, L-NAME did not augment PAF-induced venoconstriction in mouse livers. In conclusion, in rat and guinea pig livers, NO may be released selectively from the pre-sinusoids in response to PAF, and then attenuate the PAF-induced pre-sinusoidal constriction. In mouse liver, PAF-induced venoconstriction is weak and not modulated by NO.
    Prostaglandins Leukotrienes and Essential Fatty Acids 05/2007; 76(5):277-83. · 2.73 Impact Factor
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    ABSTRACT: The purpose of this study was to determine whether anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction, and the effects of anaphylaxis on hepatic segmental vascular resistances and liver weight in isolated perfused rabbit livers. The rabbits were sensitized by subcutaneous injection of antigen of 2.5 mg ovalbumin with complete Freund's adjuvant three times at 1 week interval. One week after sensitization, anaphylaxis was induced by an injection of 2.5 mg ovalbumin into the jugular vein of pentobarbital anaesthetized rabbits or the perfusate of rabbit livers perfused via the portal vein at a constant flow. Using the double occlusion technique to estimate the hepatic sinusoidal pressure, pre- (R(pre)) and post-sinusoidal (R(post)) resistances were calculated for the isolated perfused livers. An antigen injection into the sensitized rabbits caused not only a decrease in systemic arterial pressure from 79 +/- 2 to 40 +/- 4 mmHg, but also an increase in portal venous pressure (P(pv)) from 9.5 +/- 2.2 to 24.1 +/- 3.9 cmH(2)O. Portal hypertension persisted for 8 min after the antigen injection. An injection of antigen into the perfusate caused a marked increase in P(pv) from 5.4 +/- 0.1 to 28.6 +/- 2.4 cmH(2)O at 6 min, but only a slight increase in double occlusion pressure from 2.2 +/- 0.2 to 3.8 +/- 0.2 cmH(2)O, resulting in a selective increase in R(pret) rather than R(post). Concomitant with the hepatic pre-sinusoidal constriction, liver weight loss occurred. Anaphylactic hypotension in rabbits is accompanied by hepatic venoconstriction which is characterized by pre-sinusoidal contraction.
    Acta Physiologica 02/2007; 189(1):15-22. · 4.38 Impact Factor
  • Journal of Pharmacological Sciences - J PHARMACOL SCI. 01/2007; 104(3):212-217.
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    ABSTRACT: 1. The effects of the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) on anaphylaxis-induced venoconstriction were examined in rat isolated livers perfused with blood-free solutions in order to clarify the role of NO in anaphylactic venoconstriction. 2. Rats were sensitized with ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in a recirculating manner at a constant flow with Krebs'-Henseleit solution. The antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after pretreatment with L-NAME (100 micromol/L) or D-NAME (100 micromol/L) and changes in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow were monitored. In addition, concentrations of the stable metabolites of NO ( and ) were determined in the perfusate using an HPLC-Griess system. 3. The antigen caused hepatic venoconstriction, as evidenced by an increase in Ppv from a mean (SEM) baseline value of 7.7 +/- 0.1 cmH2O to a peak of 21.4 +/- 1.1 cmH2O at 3 min in D-NAME-pretreated livers. Pretreatment with L-NAME augmented anaphylactic venoconstriction, as reflected by a higher Ppv (27.4 +/- 0.8 cmH2O) after antigen than observed following D-NAME pretreatment. The addition of L-arginine, a precursor for the synthesis of NO, reversed the augmentation of anaphylactic venoconstricion by L-NAME. This suggests that hepatic anaphylaxis increased the production of NO, which consequently attenuated anaphylactic venoconstriction. However, perfusate NOx levels did not increase significantly after antigen in livers pretreated with either L-NAME or D-NAME. 4. In conclusion, L-NAME potentiates rat anaphylactic hepatic venoconstriction, suggesting that NO contributes to the attenuation of the venoconstriction. However, this functional evidence was not accompanied by corresponding changes in perfusate NOx concentrations.
    Clinical and Experimental Pharmacology and Physiology 12/2006; 33(11):1073-7. · 2.41 Impact Factor
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    ABSTRACT: Vasoconstrictive lipid mediators, thromboxane A(2) (TxA(2)), platelet-activating factor (PAF) and leukotriene D(4) (LTD(4)) have been implicated as mediators of liver diseases. There are species differences in the primary site of hepatic vasoconstriction in response to these mediators. We determined the effects of a TxA(2) analogue (U-46619), PAF and LTD(4) on the vascular resistance distribution, weight and oxygen consumption of isolated rat livers portally perfused with blood. The sinusoidal pressure was measured by the double occlusion pressure (P(do)), and was used to determine the pre- (R(pre)) and post-sinusoidal (R(post)) resistances. All these three mediators increased the hepatic total vascular resistance (R(t)). The responsiveness to PAF was 100 times greater than that to U-46619 or LTD(4). Both of PAF and U-46619 predominantly increased R(pre) over R(post). At the comparable increased R(t) levels, U-46619 more preferentially increased R(pre) than PAF. In contrast, LTD(4) increased both the R(pre) and R(post) to similar extent. U-46619 caused liver weight loss, while high concentrations of either LTD(4) or PAF produced liver weight gain, which was caused by substantial post-sinusoidal constriction and increased P(do). PAF and U-46619 decreased hepatic oxygen consumption while LTD(4) induced biphasic change of an initial transient decrease followed by an increase. In conclusion, PAF is the most potent vasoconstrictor of rat hepatic vessels among these three mediators. Both TxA(2) and PAF constrict the pre-sinusoidal veins predominantly. TxA(2) more preferentially constricts the pre-sinusoids than PAF, resulting in liver weight loss. However LTD(4) constricts both the pre- and post-sinusoidal veins similarly. High concentrations of LTD(4) and PAF cause liver weight gain by substantial post-sinusoidal constriction. PAF and TxA(2) decrease hepatic oxygen consumption, whereas LTD(4) causes a biphasic change of it.
    Prostaglandins & other lipid mediators 08/2006; 80(1-2):35-45. · 2.42 Impact Factor
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    ABSTRACT: Anaphylactic shock is accompanied by a decrease in oxygen consumption. However, it is not well known whether oxygen consumption decreases during local anaphylactic reaction in liver. We determined the effects of anaphylaxis and norepinephrine on oxygen consumption in isolated rat livers perfused portally and recirculatingly at constant flow with blood (hematocrit, 12%). Oxygen consumption was continuously measured by monitoring the portal-hepatic venous oxygen saturation differences using the absorption spectrophotometer, the probes of which were built in perfusion lines. Hepatic anaphylaxis was induced by an injection of ovalbumin (0.01 or 0.1 mg) into the perfusate of the isolated liver of the rat sensitized with subcutaneous ovalbumin (1 mg). Hepatic venoconstriction and liver weight loss were similarly observed in response to norepinephrine (0.01-10 micromol L(-1)) and anaphylaxis. However, hepatic anaphylaxis reduced oxygen consumption, whereas norepinephrine increased it. There was a possibility that anaphylactic venoconstriction could reduce the perfused surface area, resulting in decreased oxygen consumption. However, pretreatment with a vasodilator of sodium nitroprusside substantially attenuated venoconstriction but not the decrease in oxygen consumption during anaphylaxis. Thus, we conclude that local hepatic anaphylaxis decreases oxygen consumption independently of venoconstriction in isolated blood-perfused rat livers.
    Shock 08/2006; 26(1):62-8. · 2.61 Impact Factor
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    ABSTRACT: Effects of hematocrit (Hct) on N-nitro-L-arginine methyl ester (L-NAME)-induced modulation of anaphylactic venoconstriction were determined in isolated perfused rat livers. The rats were sensitized with ovalbumin (1 mg), and the livers were excised 2 weeks later and perfused portally and recirculatingly under constant flow at Hct of 0%, 5%, 16%, and 22%. The hepatic sinusoidal pressure was estimated via the double occlusion pressure (Pdo), and the presinusoidal resistance (Rpre) and the postsinusoidal resistance (Rhv) were calculated. The antigen of ovalbumin 0.1 mg was injected into the reservoir at 10 minutes after pretreatment with L-NAME (100 microM) or D-NAME (100 microM). Perfusate viscosity, a determinant of vascular resistance and shear stress, was increased in parallel with Hct. In the D-NAME groups, antigen caused predominant presinusoidal constriction. The magnitude of venoconstriction was significantly smaller at Hct 0% than at Hct 5% to 22%, whereas no significant differences were found among Hct 5% to 22%. L-NAME potentiated the antigen-induced increase in Rpre, but not in Rpost at Hct 5% to 22% as compared with D-NAME. But the augmentative effects of L-NAME were similar in magnitude among Hct 5% to 22%. These findings suggest that hepatic anaphylaxis increases production of nitric oxide, which consequently attenuates anaphylactic presinusoidal constriction in rat livers, and that these effects are independent of perfusate Hct or viscosity in blood-perfused rat livers.
    Journal of Cardiovascular Pharmacology 08/2006; 48(1):827-33. · 2.38 Impact Factor
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    ABSTRACT: The hepatic anaphylactic venoconstriction is partly involved in anaphylactic hypotension, and is characterized by significant post-sinusoidal constriction and liver congestion in guinea pigs. We determined what chemical mediators are involved in anaphylaxis-induced segmental venoconstriction and liver congestion in perfused livers isolated from ovalbumin sensitized guinea pigs. Livers were perfused portally and recirculatingly at constant flow with diluted blood. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost) resistances. An antigen injection increased both the portal vein pressure and Pdo, resulting in 4.1- and 2.3-fold increases in Rpre and Rpost, respectively. Hepatic congestion was observed as reflected by liver weight gain. Pretreatment with TCV-309 (10microM, platelet-activating factor (PAF) receptor antagonist) or ONO-1078 (100microM, human cysteinyl-leukotriene (Cys-LT) receptor 1 antagonist), but not indomethacin (10microM, cyclooxygenase inhibitor), ketanserin (10microM, serotonin receptor antagonist), or diphenhydramine (100microM, histamine H1 antagonist), significantly attenuated this anaphylactic hepatic venoconstriction. Anaphylaxis-induced increases in Rpre and Rpost were significantly inhibited by TCV-309 (by 48%) and ONO-1078 (by 36%), respectively. Combined TCV-309 and ONO-1078 pretreatment exerted additive inhibitory effects on anaphylactic hepatic venoconstriction. Anaphylactic hepatic weight gain was converted to weight loss when post-sinusoidal constriction was attenuated. It is concluded that anaphylaxis-induced pre-sinusoidal constriction is mainly caused by PAF and the post-sinusoidal constriction by Cys-LTs in guinea pig livers.
    Prostaglandins & other lipid mediators 01/2006; 78(1-4):218-30. · 2.42 Impact Factor