Rapid reversal of the effects of the portal signal under hyperinsulinemic conditions in the conscious dog.
(17/2024)
Experiments were performed on two groups of 42-h-fasted conscious dogs (n = 6/group). Somatostatin was given peripherally with insulin (4-fold basal) and glucagon (basal) intraportally. In the first experimental period, glucose was infused peripherally to double the hepatic glucose load (HGL) in both groups. In the second experimental period, glucose (21.8 micromol. kg-1. min-1) was infused intraportally and the peripheral glucose infusion rate (PeGIR) was reduced to maintain the precreating HGL in the portal signal (PO) group, whereas saline was given intraportally in the control (CON) group and PeGIR was not changed. In the third period, the portal glucose infusion was stopped in the PO group and PeGIR was increased to sustain HGL. PeGIR was continued in the CON group. The glucose loads to the liver did not differ in the CON and PO groups. Net hepatic glucose uptake was 9.6 +/- 2.5, 11.6 +/- 2.6, and 15.5 +/- 3.2 vs. 10.8 +/- 1.8, 23.7 +/- 3.0, and 15.5 +/- 1.1 micromol. kg-1. min-1, and nonhepatic glucose uptake (non-HGU) was 29.8 +/- 1.1, 40.1 +/- 4.5, and 49.5 +/- 4.0 vs. 26.6 +/- 4.3, 23.2 +/- 4.0, and 40.4 +/- 3.1 micromol. kg-1. min-1 in the CON and PO groups during the three periods, respectively. Cessation of the portal signal shifted NHGU and non-HGU to rates similar to those evident in the CON group within 10 min. These results indicate that even under hyperinsulinemic conditions the effects of the portal signal on hepatic and peripheral glucose uptake are rapidly reversible. (+info)
Splanchnic tissues undergo hypoxic stress during whole body hyperthermia.
(18/2024)
Exposure of conscious animals to environmental heat stress increases portal venous radical content. The nature of the observed heat stress-inducible radical molecules suggests that hyperthermia produces cellular hypoxic stress in liver and intestine. To investigate this hypothesis, conscious rats bearing in-dwelling portal venous and femoral artery catheters were exposed to normothermic or hyperthermic conditions. Blood gas levels were monitored during heat stress and for 24 h following heat exposure. Hyperthermia significantly increased arterial O2 saturation, splanchnic arterial-venous O2 difference, and venous PCO2, while decreasing venous O2 saturation and venous pH. One hour after heat exposure, liver glycogen levels were decreased approximately 20%. Two hours after heat exposure, the splanchnic arterial-venous O2 difference remained elevated in heat-stressed animals despite normal Tc. A second group of rats was exposed to similar conditions while receiving intra-arterial injections of the hypoxic cell marker [3H]misonidazole. Liver and intestine were biopsied, and [3H]misonidazole content was quantified. Heat stress increased tissue [3H]misonidazole retention 80% in the liver and 29% in the small intestine. Cellular [3H]misonidazole levels were significantly elevated in intestinal epithelial cells and liver zone 2 and 3 hepatocytes and Kupffer cells. This effect was most prominent in the proximal small intestine and small liver lobi. These data provide evidence that hyperthermia produces cellular hypoxia and metabolic stress in splanchnic tissues and suggest that cellular metabolic stress may contribute to radical generation during heat stress. (+info)
Peptidyl inhibitors of shaker-type Kv1 channels elicit twitches in guinea pig ileum by blocking kv1.1 at enteric nervous system and enhancing acetylcholine release.
(19/2024)
Potent and selective peptidyl blockers of the Shaker-type (Kv1) voltage-gated potassium channels were used to determine the role of these channels in regulating the spontaneous motility of smooth muscle preparations. Margatoxin (MgTX), kaliotoxin, and agitoxin-2 at 1 to 10 nM and agitoxin-1 at 50 to 100 nM induce twitches in guinea pig ileum strips. These twitches are abolished by tetrodotoxin (TTX, 0.5 microM), atropine (1 microM), hexamethonium (10 microM), or nifedipine (0.1 microM). It is proposed that blockade of Kv1 channels by MgTX, kaliotoxin, or the agitoxins increases excitability of intramural nerve plexuses in the ileum, promoting release of acetylcholine from excitatory motor nerve terminals. This, in turn, leads to Ca2+-dependent action potentials and twitching of the muscle fibers. MgTX does not induce twitches in several other guinea pig and/or rat vascular, genitourinary, or gastrointestinal smooth muscles, although small increases in spontaneous myogenic activity may be seen in detrusor muscle exposed to >30 nM MgTX. This effect is not reversed by TTX or atropine. The TTX- and atropine-sensitive twitches of guinea pig ileum are also induced by nanomolar concentrations of alpha-dendrotoxin, a selective blocker of Shaker Kv1.1 and 1.2 subtypes, or stichodactylatoxin, a peptide isolated from sea anemone that displays high affinity for Kv1.1 and 1.3, but not by charybdotoxin, which blocks Kv1.2 and 1.3 but not 1.1. The data taken together suggest that high-affinity blockade of Kv1.1 underlies the ability of MgTX, kaliotoxin, agitoxin-1, agitoxin-2, alpha-dendrotoxin, and stichodactylatoxin to elicit TTX-sensitive twitches in guinea pig ileum. (+info)
Hepatic artery flow and propranolol metabolism in perfused cirrhotic rat liver.
(20/2024)
The oxygen limitation theory states that capillarization of the sinusoidal endothelium in cirrhosis impairs hepatocellular oxygen uptake manifesting as a reduction in oxygen-dependent enzyme activity including phase 1 drug metabolism. The hepatic artery supplies highly oxygenated blood to the liver. Therefore, we tested whether augmentation of hepatic arterial blood flow could improve hepatic oxygenation and function in cirrhosis. Rats were treated with carbon tetrachloride and phenobarbitone to induce hepatic cirrhosis or fibrosis. We used a bivascular rat liver perfusion model to examine the effects of increased hepatic artery flow on propranolol clearance and oxygen consumption. Each liver was perfused at three hepatic artery flow rates, 1 to 3, 4 to 6, and 7 to 9 ml/min with a constant portal venous flow of 7 to 9 ml/min. Increasing the hepatic artery flow led to improvement in propranolol clearance in control (n = 7, P <.001), fibrotic (n = 8, P <.001), and cirrhotic (n = 6, P <.001) livers. Intrinsic clearance of propranolol increased only in the cirrhotic livers (P =.01), indicating an improvement in enzyme activity. Regression analysis indicated that this improvement was mediated by change in oxygen delivery alone (P =.001). The results confirm that propranolol metabolizing enzyme activity in cirrhosis can be improved by increasing oxygen delivery by increasing hepatic arterial blood flow. These findings suggest that increasing hepatic arterial blood flow may be an important therapeutic strategy for improving global liver function in cirrhosis. (+info)
Chronic ethanol consumption induces hypomotility in the portal vein of Sardinian alcohol-preferring rats.
(21/2024)
In order to study the physiopathological effects of chronic ethanol intake on the smooth muscle of the vascular system, we have assessed the length-tension relationship in isolated portal veins of Sardinian alcohol-preferring (sP) rats. Significant differences in motor performance were found between sP naive and sP rats exposed to ethanol consumption (12% w/v) for 48 weeks. Isolated portal veins of sP rats which consumed ethanol chronically showed a marked decrease of spontaneous and KCl-induced contraction waves when compared to sP naive rats. At optimum length (140% Lr) for maximal contractile performance, the mean amplitude wave in the portal veins of sP drinker rats was about five times less than in sP naive veins. Furthermore, in the veins of sP drinkers, the active curve showed lower values of tension at each elongation of the vascular segment, the maximum value of active tension (7.32 +/- 0.54 mN) represented a reduction in amplitude of about 32% with respect to sP naive veins. These results indicate that long-term ethanol consumption impairs portal vein motility. (+info)
Isozyme-specific inhibitors of protein kinase C translocation: effects on contractility of single permeabilized vascular muscle cells of the ferret.
(22/2024)
1. The effects on contractility of three peptides reported to inhibit protein kinase C (PKC) translocation in an isozyme-specific manner were studied: a peptide from the C2 domain of conventional PKCs (C2-2), a peptide from the N-terminal variable domain of epsilonPKC (epsilonV1-2) and a peptide (ABP) from the actin-binding domain of epsilonPKC (epsilon(223-228)). 2. Isometric force was directly recorded from individual hyperpermeable ferret portal vein or aortic smooth muscle cells. 3. Phenylephrine contracted permeabilized portal vein cells at pCa 6.7 but not at pCa 7.0. However, phenylephrine did contract aortic cells at pCa 7.0. 4. C2-2 inhibited phenylephrine-induced contraction, but did not affect resting tension, in portal vein cells at pCa 6.7. In aortic cells at either pCa 6.7 or 7.0, C2-2 had no effect on either basal tension or phenylephrine-induced contraction. 5. ABP did not evoke any changes in phenylephrine-induced contraction or baseline tension in either portal vein or aortic cells. 6. epsilonV1-2 inhibited phenylephrine-induced contraction and decreased resting tension in aortic cells at pCa 7.0, but not in portal vein cells at pCa 6.7. 7. Western blots indicated that portal vein cells contained substantially more alphaPKC than aortic cells. Portal vein cells also contained small amounts of betaPKC, which was undetectable in aortic cells. In contrast, aortic cells contained more epsilonPKC than portal vein cells. Even though epsilonPKC was expressed in portal vein and alphaPKC in aorta, imaging studies indicated that they were not translocated in these cell types. 8. These results suggest that the Ca2+-dependent isozymes of PKC (alpha and/or beta) play a major role in contraction of the portal vein but not of the aorta. In contrast, the results are consistent with epsilonPKC, but not Ca2+-dependent PKC isozymes, regulating contractility of the aorta. (+info)
Ultrasonographic arterial portography with second harmonic imaging: evaluation of hepatic parenchymal enhancement with portal venous flow.
(23/2024)
Ultrasonographic arterial portography was evaluated with second harmonic and conventional gray scale imaging after the administration of 0.001 to 0.1 ml/kg of FS069 (Optison) in 10 dogs (four dogs with ligation of the portal vein branch) and two woodchucks with hepatocellular carcinomas. Harmonic imaging was required to obtain good liver parenchymal enhancement for ultrasonographic arterial portography to be useful. The tumors were visible as regions of greater enhancement after intravenous injection and as hypoechoic regions after superior mesenteric artery injection. The segments with portal vein ligation were not detected after intravenous injection but were clearly seen after superior mesenteric artery injection. Doppler signal measurement verified a significant difference between the portal vein and hepatic vein after superior mesenteric artery injection and in the femoral artery after intravenous versus superior mesenteric artery injection, demonstrating that minimal levels of FS069 pass through the liver. (+info)
Portal venous system aneurysms: report of five cases.
(24/2024)
Until recently aneurysms in the portal venous system were considered to be very rare lesions. This opinion has largely been changed by the increasing number of cases reported in recent years. In this paper we report the cases of five patients with portal venous system aneurysms, including one with splenic vein aneurysm. One patient had associated portal hypertension. The reexamination of two patients 2 years later showed no change in the aneurysms. The sonographic features and related literature are reviewed. In the light of this series and the information in the literature, we recommend that portal venous system aneurysms should no longer be considered exceptionally rare entities. (+info)