Hepatic microvascular regulatory mechanisms. I. Adrenergic mechanisms

Reilly, Frank; McCuskey, Robert S.; Cilento, Eugene V.

doi:10.1016/0026-2862(81)90008-x

Cited by 79 publications

(43 citation statements)

References 21 publications

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“…10). Verapamil could exert these effects by acting on endothelial cells, the main determinants of sinusoidal perfusion (36,37). Verapamil is known to affect all smooth muscle cells (9), including those of rat portal vein (38); it is unknown, however, whether verapamil affects hepatic endothelial cells.…”

Section: Resultsmentioning

confidence: 99%

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Reichen¹,

Le²

1986

J. Clin. Invest.

131

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The effect of the calcium channel blocking agent, verapamil, on microcirculatory patterns and hepatic function was investigated in the perfused liver of cirrhotic rats. Compared with controls, cirrhotic livers had higher vascular resistance, increased intrahepatic shunting, and smaller extravascular albumin space and larger extravascular sucrose space, as determined by a multipleindicator dilution technique. Hepatic function, estimated by determining propranolol and antipyrine extraction, was markedly reduced in cirrhotic livers. Portal pressure was then reduced 25% either pharmacologically by verapamil or hydrodynamically by lowering inflow. Verapamil decreased vascular resistance by 22%. This was associated with a 38% reduction in intrahepatic shunting and a 62% increase in extravascular albumin space. Hydrodynamically lowering pressure had no or adverse effects. The verapamil-induced improvement in microcirculatory characteristics was associated with a significant improvement in oxygen consumption (+21%) and antipyrine clearance (+20%). We conclude that the microvascular distortions of liver cirrhosis in the rat are partially reversible by vasodilators like verapamil.

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Section: Resultsmentioning

confidence: 99%

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Reichen¹,

Le²

1986

J. Clin. Invest.

131

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“…To determine the diameter of hepatic sinusoids and to confirm the state of microvascular perfusion, 2.0% solution of FITC-BSA was injected into the perfusion circuit at a rate of 250 il/s for 4 s. The intralobular movement of the fluorescence tracer was visualized by epi-illuminating at 480 nm with passage through a 530-nm emission filter (BA520; Nikon), and was recorded continuously to a digital videorecorder (Sflow, Kista, Sweden) (9, 10), the intralobular perfusion velocity (Vpc) vation period, such an experiment was discarded to avoid data from low quality preparations which mainly resulted from local perfusion failure. In another set of experiments, the a1-adrenergic receptor agonist phenylephrine (PE) was used as the positive control, since adrenergic nerve endings (12) and catecholamine-mediated constriction are localized to the portal venules in the rat (13). The whole organ vascular resistance in the liver was estimated as the ratio of the pressure gradient between the portal and hepatic veins versus flow volume according to the previous method (14).…”

Section: Methodsmentioning

confidence: 99%

Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver.

et al. 1995

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Heme oxygenase is a heme-oxidizing enzyme which generates biliverdin and carbon monoxide (CO). The present study was designed to elucidate whether CO endogenously produced by this enzyme serves as an active vasorelaxant in the hepatic microcirculation. Microvasculature of the isolated perfused rat liver was visualized by dual-color digital microfluorography to alternately monitor sinusoidal lining and fat-storing Ito cells. In the control liver, the CO flux in the venous effluent ranged at 0.7 nmol/min per gram of liver. Administration of a heme oxygenase inhibitor zinc protoporphyrin IX (1 ,uM) eliminated the baseline CO generation, and the vascular resistance exhibited a 30% elevation concurrent with discrete patterns of constriction in sinusoids and reduction of the sinusoidal perfusion velocity.The major sites of the constriction corresponded to local sinusoidal segments colocalized with Ito cells which were identified by imaging their vitamin A autofluorescence. The increase in the vascular resistance and sinusoidal constriction were attenuated significantly by adding CO (1 ,uM) or a cGMP analogue 8-bromo-cGMP (1 ,uM) in the perfusate. From these findings, we propose that CO can function as an endogenous modulator of hepatic sinusoidal perfusion through a relaxing mechanism involving Ito cells. (J. Clin. Invest. 1995. 96:2431-2437

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“…This suggests that norepinephrine causes sinusoidal constriction. Reilly et al (20) reported that the small but significant decrease in sinusoidal diameter was observed when ␣-adrenergic receptors were stimulated. Although sinusoids do not contain smooth muscle cells, hepatic stellate cells, which are contractile and located around the sinusoidal endothelial cells, might reduce the diameter of sinusoids if it could contract in response to norepinephrine (25).…”

Section: H127mentioning

confidence: 99%

Effects of Hct and norepinephrine on segmental vascular resistance distribution in isolated perfused rat livers

Kamikado¹,

Shibamoto²,

Hongo³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Kamikado, Chiaki, Toshishige Shibamoto, Minoru Hongo, and Shozo Koyama. Effects of Hct and norepinephrine on segmental vascular resistance distribution in isolated perfused rat livers. Am J Physiol Heart Circ Physiol 286: H121-H130, 2004. First published August 28, 2003 10.1152/ajpheart.01136.2002We studied the effects of blood hematocrit (Hct), blood flow, or norepinephrine on segmental vascular resistances in isolated portally perfused rat livers. Total portal hepatic venous resistance (R t) was assigned to the portal (R pv), sinusoidal (Rsinus), and hepatic venous (Rhv) resistances using the portal occlusion (P po) and the hepatic venous occlusion (Phvo) pressures that were obtained during occlusion of the respective line. Four levels of Hct (30%, 20%, 10%, and 0%) were studied. R pv comprises 44% of Rt, 37% of Rsinus, and 19% of Rhv in livers perfused at 30% Hct and portal venous pressure of 9.1 cmH 2O. As Hct increased at a given blood flow, all three segmental vascular resistances of R pv, Rsinus, and Rhv increased at flow Ͼ15 ml/min. As blood flow increased at a given Hct, only R sinus increased without changes in R pv or Rhv. Norepinephrine increased predominantly Rpv, and, to a smaller extent, R sinus, but it did not affect Rhv. Finally, we estimated P po and Phvo from the double occlusion maneuver, which occluded simultaneously both the portal and hepatic venous lines. The regression line analysis revealed that P po and Phvo were identical with those measured by double occlusion. In conclusion, changes in blood Hct affect all three segmental vascular resistances, whereas changes in blood flow affect R sinus, but not Rpv or Rhv. Norepinephrine increases mainly presinusoidal resistance. P po and Phvo can be obtained by the double occlusion method in isolated perfused rat livers. blood viscosity; hepatic circulation; hepatic vascular occlusion methods LIVER AND LUNG circulation is analogous (19). Both the pulmonary artery and the portal vein are unique in their ability to carry large flows of venous blood under low hydrostatic pressures. The pulmonary arterioles and the portal venules have a similar anatomy (19). The vascular arrangement of the hepatic units is analogous to that of the lung in that both lobules have a central inflow (pulmonary artery and portal vein) and a peripheral outflow (pulmonary vein and hepatic vein) (18). In addition, embryologically, the tracheo-bronchial tree and the biliary ductal system originate from the gut.The longitudinal distribution of pulmonary vascular resistance has been extensively studied using vascular occlusion techniques, and the pulmonary vasculature can be represented by a simple hydrodynamic model consisting of three segments in series, each with a characteristic resistance and compliance (10, 12). The middle segment, which contains the capillaries, has relatively low resistance and high compliance, and the other two segments have relatively low compliance and high resistance. The pulmonary arterial and venous occlusion technique (9-11) allows partitioning ...

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Hepatic microvascular regulatory mechanisms. I. Adrenergic mechanisms

Cited by 79 publications

References 21 publications

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver.

Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver.

Effects of Hct and norepinephrine on segmental vascular resistance distribution in isolated perfused rat livers

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