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In splanchnic arteries, vasodilators decrease the cytosolic free calcium concentration ([Ca2+]i) by inducing Ca2+sequestration and extrusion, by limiting the entry of extracellular Ca2+via L-type Ca2+channels and by decreasing the agonist-induced mobilization of intracellular Ca2+. Cyclic GMP kinase and membrane hyperpolarization are important mediators of the decrease in [Ca2+]i. Vasoconstrictors increase [Ca2+]i by mobilizing intracellular Ca2+from the sarcoplasmic reticulum and by stimulating extracellular Ca2+entry via L-type Ca2+channels. Activation of G proteins, inositol trisphosphate, diacylglycerol and membrane depolarization are important mediators of the increase in [Ca2+]i.

A somatostatin analogue, a long-acting octapeptide (SMS 201-995), has been reported to decrease portal pressure, but the mechanism is unclear. To elucidate the effects of this drug on both systemic and splanchnic hemodynamics, it was administered in two conscious rat models of portal hypertension. The dose-response curves showed that the somatostatin analogue significantly decreased portal pressure at a lower dose in rats with cirrhosis than in portal vein-stenosed rats. Calculated ED50values were significantly different among all groups. Intravenous infusion of 8 μg/kg body wt · h of somatostatin analogue significantly decreased cardiac output by ~20% in both groups of portal hypertensive rats and increased mean arterial pressure by 7%. Accordingly, systemic vascular resistance markedly increased, indicating vasoconstrictor effects of this drug. The somatostatin analogue also significantly decreased portal tributary blood flow by 18% in portal vein-stenosed rats and 27% in cirrhotic rats. In sham-operated rats, somatostatin analogue had no effect on the systemic or splanchnic circulation. This study shows that somatostatin analogue decreases portal pressure principally by reducing portal tributary blood flow. This reduction may be due to either a direct vasoconstrictive effect or diminution in vasoactive hormone release.

Liver involvement is common in acute and chronic Q fever and consists of nonspecific hepatitis and granulomas without fibrosis. We report the case of a patient suffering from chronic Q fever with nonspecific hepatitis and granulomas, in whom progressive development of extensive liver fibrosis was documented by repeated biopsies.

Catecholamines, which are elevated during alcohol withdrawal, can alter hepatic blood flow and increase hepatic oxygen consumption. We hypothesized that, in the withdrawal state, hepatic oxygen consumption and delivery could be altered in relation to an increased sympathetic activity. Thirteen chronic alcoholics were studied 34–72 h after withdrawal and 10 days later (control period) using conventional hemodynamic methods. As compared with the control period, splanchnic oxygen uptake was elevated at withdrawal (74.5 ± 27.1 vs. 59.2 ± 16.8 ml/min, p < 0.025) and its variation was correlated with that of plasma epinephrine (r = 0.70, p < 0.01). The hepatic venous oxygen content was reduced at withdrawal (113 ± 22 vs. 126 ± 21 ml/L, p < 0.025) and correlated inversely with plasma norepinephrine levels (r = 0.56, p < 0.01). We conclude that, during alcohol withdrawal in humans, hepatic energy expenditure may be elevated in relation to epinephrine secretion and that sympathetic overactivity may hinder the adaptive response in hepatic blood flow. The wide range in sympathetic nervous response to alcohol withdrawal could explain some differences in individual susceptibility to liver damage caused by alcohol.

To elucidate a possible role for reduction of intrahepatic vascular space in the pathogenesis of portal hypertension, we studied a partially hepatectomized rat model in vitro and in vivo. The in vitro study used livers from normal, ⅓-hepatectomized, and 2/3-hepatectomized rats, and rats with cirrhosis caused by chronic bile duct ligation, for isolated, perfused flow-pressure plotting. Resistance to perfusion increased such that significant differences were found between all groups except the last two, which showed similar resistances. The in vivo study measured splanchnic blood flow by radioactive microspheres and portal pressure in anesthetized shamoperated and ⅓- and 2/3-hepatectomized rats. Although absolute portal tributary blood flows did not change, portal flow per gram of remnant liver showed significant increases: 1.57 ± 0.32 ml/min · g liver, 2.52 ± 0.60 ml/min · g liver, p < 0.01; 3.48 ± 1.04 ml/min · g liver, p < 0.01, respectively. Although intrahepatic resistance increased significantly only in the 2/3-hepatectomized group, portal pressures increased significantly in both groups of hepatectomized rats: normal, 7.5 ± 1.1 mmHg; ⅓-hepatectomized, 9.4 ± 1.1 mmHg; and 2/3-hepatectomized, 11.1 ± 1.2 mmHg. Thus, decreased intrahepatic vascular space caused by resection and hepatocellular hypertrophy leads to portal hypertension, thereby suggesting that this reduction in space may be the pathogenic factor common to a number of different theories of portal hypertension.

1. Basal forearm haemodynamics were studied by venous occlusion plethysmography in three groups of subjects: group I, healthy controls, group II, patients with cirrhosis age- and sex-matched with group I, and group III, an older group of patients with cirrhosis. Subsequently, responses to sublingual nitroglycerin were measured in group I and II subjects. 2. Controls responded to nitroglycerin with an increase in venous distensibility; group II patients had higher initial venous distensibility but did not respond to nitroglycerin. No other variables in either group were affected by nitroglycerin. 3. Group II and III patients differed in forearm blood flow and vascular resistance and venous distensibility. A significant inverse correlation was found between age and forearm blood flow (r = −0.57, P < 0.001) in all patients with cirrhosis. 4. We conclude that (a) venous tone is reduced in cirrhosis, possibly as a result of chronic venodilatation; (b) this venodilatation impedes further dilatory response to a small dose of nitroglycerin; (c) cirrhosis is also associated with age-related decreases in peripheral haemodynamics.