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ABSTRACT: ABSTRACT Systemic anaphylaxis accompanies pulmonary vasoconstriction and bronchoconstriction, which may contribute to increased right heart afterload, and finally anaphylactic hypotension. However, the pulmonary response to anaphylaxis is not known in mice. We determined the pulmonary vascular and bronchial response to systemic anaphylaxis in anesthetized BALB/c mice. We also clarified the roles of β-adrenoceptors, nitric oxide, and cyclooxygenase metabolites in these responses. Anaphylaxis was induced by an intravenous injection of the ovalbumin antigen into open-chest artificially ventilated sensitized mice. Mean arterial pressure, systolic pulmonary arterial pressure, central venous pressure, airway pressure, and aortic blood flow were continuously measured. In sensitized control mice, mean arterial pressure, and aortic blood flow substantially decreased soon after the antigen injection, while systolic pulmonary arterial pressure and airway pressure did not increase. In contrast, in mice pretreated with either the β(2)-adrenoceptor antagonist ICI 118,551 (0.2 mg/kg; n = 6), or L-NAME (50 mg/kg; n = 6), but not with the β(1)-adrenoceptor antagonist atenolol (2 mg/kg; n = 6) or indomethacin (5 mg/kg; n = 6), systolic pulmonary arterial pressure increased by 7 mmHg at 1.5 min after antigen. In L-NAME pretreated mice, pulmonary hypertension was sustained over 30 min of the experimental period. Airway pressure did not significantly change after antigen in any mice studied. In conclusion, pulmonary response to systemic anaphylaxis does not increase the right heart afterload and, therefore, may not contribute to the initial decrease in venous return and anaphylactic hypotension in anesthetized mice. β(2)-adrenoceptor activation and nitric oxide, but not β(1)-adrenoceptor activation or cyclooxygenase metabolites, attenuate the antigen-induced pulmonary vasoconstriction.
Experimental Lung Research 02/2013; · 1.22 Impact Factor
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ABSTRACT: To determine fluid extravasation in the splanchnic vascular bed during anaphylactic hypotension, the mesenteric lymph flow (Q(lym)) was measured in anesthetized rats sensitized with ovalbumin, along with the systemic arterial pressure (P(sa)) and portal venous pressure (P(pv)). When the antigen was injected into the sensitized rats (n = 10), P(sa) decreased from 125 ± 4 to 37 ± 2 mmHg at 10 min with a gradual recovery, whereas P(pv) increased by 16 mmHg at 2 min and returned to the baseline at 10 min. Q(lym) increased 3.3-fold from the baseline of 0.023 ± 0.002 g/min to the peak levels of 0.075 ± 0.009 g/min at 2 min and returned to the baseline within 12 min. The lymph protein concentrations increased after antigen, a finding indicating increased vascular permeability. To determine the role of the P(pv) increase in the antigen-induced increase in Q(lym), P(pv) of the nonsensitized rats (n = 10) was mechanically elevated in a manner similar to that of the sensitized rats by compressing the portal vein near the hepatic hilus. Unexpectedly, P(pv) elevation alone produced a similar increase in Q(lym), with the peak comparable to that of the sensitized rats. This finding aroused a question why the antigen-induced increase in Q(lym) was limited despite the presence of increased vascular permeability. Thus the changes in splanchnic vascular surface area were assessed by measuring the mesenteric arterial flow. The mesenteric arterial flow was decreased much more in the sensitized rats (75%; n = 5) than the nonsensitized P(pv) elevated rats (50%; n = 5). In conclusion, mesenteric lymph flow increases transiently after antigen presumably due to increased capillary pressure of the splanchnic vascular bed via downstream P(pv) elevation and perfusion and increased vascular permeability in anesthetized rats. However, this increased extravasation is subsequently limited by decreases in vascular surface area and filtration pressure.
AJP Regulatory Integrative and Comparative Physiology 03/2012; 302(10):R1191-6. · 3.34 Impact Factor
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ABSTRACT: Vasopressin, a vasoactive peptide, causes vasoconstriction via V1a vasopressin receptors. Unlike other vasoconstrictor agents, vasopressin also has vasodilatory properties. The purpose of this study was to determine the effect of vasopressin on hepatic and splanchnic circulation in Sprague- Dawley rats. The experiments were conducted in not only isolated blood- and constant flowperfused livers but also anesthetized spontaneously breathing rats. In anesthetized rats, portal venous pressure (Ppv), systemic arterial pressure (Psa), central venous pressure, and hepatic blood flow (HBF) of combined portal venous and hepatic arterial blood flow were continuously measured, and splanchnic vascular bed resistance (Rspl) defined by (Psa - Ppv) / HBF was determined. In perfused livers, vasopressin at 0.1-1,000 nM caused weak venoconstriction as evidenced by small increase in Ppv. In anesthetized rats, when vasopressin was injected into the portal vein as a bolus consecutively at 0.01-100 nmol/kg, Psa increased dose-dependently with the peak increment of 60 ± 18 mmHg at 100 nmol/kg. Ppv and HBF decreased, with resultant increase in Rspl, indicating splanchnic vasoconstriction. In conclusion, hepatic venoconstrictor action of vasopressin was weak in rats. Vasopressin causes splanchnic vasoconstriction, resulting in a decrease in HBF and Ppv in anesthetized rats.
Biomedical Research 01/2012; 33(2):83-8. · 1.15 Impact Factor
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ABSTRACT: Patients treated with propranolol, a nonselective β-adrenoceptor antagonist, have increased incidence and severity of anaphylaxis. We determined whether β1- or β2-adrenoceptor antagonist modulated pulmonary vasoconstriction and bronchoconstriction in rat anaphylactic hypotension.
Anesthetized ovalbumin-sensitized male Sprague-Dawley rats were randomly allocated to the following pretreatment groups (n = 7/group): (1) sensitized control (nonpretreatment), (2) propranolol, (3) the selective β2-adrenoceptor antagonist ICI 118,551, (4) the selective β1-adrenoceptor antagonist atenolol, and (5) adrenalectomy. Shock was induced by an intravenous injection of the antigen. Mean arterial pressure, pulmonary arterial pressure, left atrial pressure, central venous pressure, portal venous pressure, airway pressure, and aortic blood flow were continuously measured.
In either sensitized control or atenolol-pretreated rats, mean arterial pressure and aortic blood flow decreased substantially, whereas pulmonary arterial pressure and airway pressure did not increase soon after antigen injection. In contrast, in rats pretreated with either propranolol, ICI 118,551, or adrenalectomy, airway pressure significantly increased by 14 cm H2O, and pulmonary arterial pressure by 7.5 mmHg after antigen injection. At 2.5 min after antigen injection, the plasma concentration of epinephrine increased 14-fold in the sensitized rats except for the adrenalectomy group. Portal venous pressure after antigen injection increased by 16 mmHg similarly in all sensitized rats. All of the sensitized control group and two of the atenolol group were alive for 60 min after antigen injection, whereas all rats of the propranolol, ICI 118,551, and adrenalectomy groups died within 50 min after antigen injection.
The pulmonary vasoconstrictive and bronchoconstrictive responses to systemic anaphylaxis were weakened via β2-adrenoceptor activation by epinephrine endogenously released from the adrenal gland in the anesthetized Sprague-Dawley rats.
Anesthesiology 03/2011; 114(3):614-23. · 5.36 Impact Factor
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ABSTRACT: Anaphylactic shock in rats is characterized by antigen-induced hepatic venoconstriction and the resultant portal hypertension. We determined the role of portal hypertension in anaphylactic hypotension by using the side-to-side portacaval shunt- and sham-operated rats sensitized with ovalbumin (1 mg). We measured the mean arterial blood pressure (MAP), portal venous pressure (PVP), and central venous pressure (CVP) under pentobarbital anesthesia and spontaneous breathing. Anaphylactic hypotension was induced by an intravenous injection of ovalbumin (0.6 mg). In sham rats, the antigen caused not only an increase in PVP from 11.3 cmH(2)O to the peak of 27.9 cmH(2)O but also a decrease in MAP from 103 mmHg to the lowest value of 41 mmHg. CVP also decreased significantly after the antigen. In the portacaval shunt rats, in response to the antigen, PVP increased slightly, but significantly, to the peak of 17.5 cmH(2)O, CVP did not decrease, and MAP decreased to a lesser degree with the lowest value being 60 mmHg. These results suggest that the portacaval shunt attenuated anaphylactic portal hypertension and venous return decrease, partially preventing anaphylactic hypotension. In conclusion, portal hypertension is involved in rat anaphylactic hypotension presumably via splanchnic congestion resulting in decreased venous return and thus systemic arterial hypotension.
The Journal of Physiological Sciences 03/2011; 61(2):161-6. · 1.61 Impact Factor
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ABSTRACT: It is reported that mast cells are involved in ischemia-reperfusion (I/R) injury of several organs such as intestine, heart, and brain in rats. However, the roles of mast cells are not known in rat hepatic I/R injury. We determined using genetically mast cell deficient (Ws/Ws) rats whether mast cells participate in the genesis of hepatic I/R injury.
Isolated livers from male Ws/Ws rats (n = 6), their wild type +/+ rats (n = 6), and Sprague Dawely (SD) rats (n = 12) were perfused portally with diluted blood (Hct 8%) at a constant blood flow. 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 pre- and post-sinusoidal resistances were determined by measuring the portal venous pressure (Ppv), hepatic venous pressure, blood flow and the sinusoidal pressure, which was assessed by the double occlusion pressure (Pdo). Liver injury was assessed by blood alanine aminotransferase (ALT) levels, bile flow rate and histology of the livers.
In the +/+ group, liver injury occurred after reperfusion; blood ALT levels increased from 19 ± 4 (SD) to 71 ± 18 and 135 ± 30 (IU/L) at 30 and 60 min, respectively, and bile flow decreased to 51% ± 6% of the baseline at 60 min after reperfusion. Histologic examination revealed marked hepatic degeneration. Similar changes were observed in the Ws/Ws rats and the SD rats (n = 6), and there were no significant differences in the variables among the Ws/Ws, +/+, and SD groups. In any ischemia groups, immediately after reperfusion, Ppv substantially, but Pdo only slightly, increased, followed by a return towards the baseline, indicating a predominant increase in pre-sinusoidal resistance over post-sinusoidal resistance. Liver weight significantly increased at 60 min after reperfusion. In the control SD rats without I/R (n = 6), no significant changes were observed in the variables.
I/R injury occurs in the absence of hepatic mast cells in the isolated perfused rat liver model of I/R injury.
Journal of Surgical Research 12/2010; 174(1):114-9. · 2.25 Impact Factor
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ABSTRACT: Ethanol constricts hepatic vessels of isolated perfused livers of rats, but not dogs. However, it is not known whether ethanol constricts or dilates the hepatic vessels in other species such as guinea pigs and mice. In addition, the sites of hepatic venoconstriction induced by ethanol were not known in rat livers. We therefore studied the effects of ethanol on the segmental hepatic vascular resistance and liver weight of mice, rats and guinea pigs.
The isolated livers were portally perfused with diluted blood at constant flow. The sinusoidal pressure was measured by the double occlusion method and was used to determine the pre- and post-sinusoidal resistance. The change of liver weight was also measured. Ethanol was administered cumulatively into the perfusate to gain clinically relevant concentrations of 1-300 mM.
Ethanol dose dependently caused predominant pre-sinusoidal constriction in livers of all three species. When compared with the livers of the guinea pigs and rats, the mouse livers were the weakest in response. Dose-dependent decreases in liver weight and bile flow accompanied predominant pre-sinusoidal constriction in guinea pigs and rats.
Ethanol predominantly constricts pre-sinusoids in rat, guinea pig and mouse livers, although the mouse liver response was much weaker. Ethanol-induced pre-sinusoidal constriction is accompanied by reduction of liver blood volume in guinea pigs and rats.
Alcohol and Alcoholism 46(2):117-22. · 2.95 Impact Factor
