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A Albillos

Publications and source records attributed to A Albillos.

At least 73 records · Page 4Linked to original sources
PubMed1994

Modulation by L-type Ca2+ channels and apamin-sensitive K+ channels of muscarinic responses in cat chromaffin cells.

In the perfused cat adrenal gland stimulated with the muscarinic agonist methacholine chloride (100 microM for 3 min), two components were detected in the catecholamine secretory response: 1) an early phasic component that peaked at 300 ng/5 s catecholamine release and 2) a tonic component whose peak was transient and declined to a plateau of about 140 ng/5 s. Apamin (0.1 microM) increased the phasic component to 1,200 ng/5 s and the tonic component to approximately 350 ng/5 s. In single fura 2-loaded cat adrenal chromaffin cells, the cytosolic Ca2+ concentration ([Ca2+]i) also followed a biphasic pattern after stimulation with methacholine. Depletion of extracellular Ca2+ reduced the phasic [Ca2+]i peak by > 50% and the phasic secretory peak by approximately 90%; both the tonic components of [Ca2+]i and secretion were abolished. Depletion of intracellular Ca2+ pools decreased the phasic and tonic components of [Ca2+]i and secretion with respect to control values; however, the phasic components diminished more than the tonic components of [Ca2+]i and secretion. Although 3 microM furnidipine (a dihydropyridine L-type Ca2+ channel blocker) inhibited the phasic component of [Ca2+]i and secretion, its effects were more pronounced on the tonic component. omega-Conotoxin GVIA (1 microM, an N-type Ca2+ channel blocker) did not affect the [Ca2+]i or the methacholine secretory responses. The secretion peak seems to depend on both extracellular free Ca2+ (Cao2+) entry through L-type Ca2+ channels as well as on the mobilization of Ca2+ from intracellular stores; the plateau depends only on Cao2+ entry through L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1994

Hemodynamic effects of alpha-adrenergic blockade with prazosin in cirrhotic patients with portal hypertension.

This study was aimed at investigating whether the blockade of alpha 1-adrenergic receptors could reduce portal pressure in cirrhosis. Splanchnic and systemic hemodynamics were measured in 12 cirrhotic patients with esophageal varices at baseline and 1 hr after oral administration of 2 mg of prazosin (acute study). Measurements were repeated in 10 of these 12 patients after a 3-mo course of 5 mg/12 hr of prazosin (long-term study). Short-term prazosin significantly lowered the hepatic venous pressure gradient from 20.1 +/- 1.3 to 14.4 +/- 0.9 mm Hg (-25.7%) (p < 0.01), and chronic prazosin reduced it to 16.5 +/- 1.3 mm Hg (-19.1%) (p < 0.01). Hepatic blood flow was increased, thus changes in the hepatic venous pressure gradient resulted from a reduction in the estimated hepatic vascular resistance. Reductions in hepatic venous pressure gradient achieved after short-term and long-term prazosin were not significantly different. Reductions in mean arterial pressure and systemic vascular resistance were significantly greater after short-term than after long-term prazosin. Long-term prazosin was associated with significant increases in hepatic and intrinsic hepatic clearances of indocyanine green. This therapy also led to an increase in pulmonary capillary pressure (+ 28.6%, p < 0.05) and body weight (+ 3.06%, p < 0.01) and a decrease in hematocrit (-6.1%, p < 0.05) and urinary sodium excretion (-22.6%, p < 0.05). In contrast, there were no hemodynamic changes in a group of six cirrhotic patients receiving placebo. In cirrhotic patients, short-term prazosin lowers portal pressure by decreasing hepatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1993

omega-Agatoxin-IVA-sensitive calcium channels in bovine chromaffin cells.

A large component of the whole-cell currents through Ca2+ channels in bovine adrenomedullary chromaffin cells has been shown to be insensitive to both L-type and N-type Ca2+ channel blockers, suggesting the existence of a third type of Ca2+ channel. In the present paper, omega-agatoxin-IVA (AgTx), a selective blocker of P-type Ca2+ channels in mammalian neurons, has been used to investigate the presence of this subtype of Ca2+ channel in bovine chromaffin cells. Barium currents (IBa) through Ca2+ channels were recorded in whole-cell patch-clamped bovine chromaffin cells. IBa was blocked by AgTx in a dose-dependent and irreversible manner. At the maximal concentration used (1 microM), AgTx inhibited IBa by 49.5 +/- 3%. Such a blockade was also present when bovine chromaffin cells were pretreated with 10 microM furnidipine, a novel 1,4-dihydropyridine L-type channel blocker, and after treatment with 1 microM of the N-type channel blocker, omega-conotoxin GVIA (CgTx). A combination of these three types of Ca2+ channel blockers suppressed the macroscopic Ba2+ currents by 88%. We conclude that bovine chromaffin cells, in addition to N- and L-type Ca2+ channels, possess a P-like component in their whole-cell currents through the Ca2+ channels.

Adrenal Medulla↗
PubMed1993

Bovine chromaffin cells possess FTX-sensitive calcium channels.

The effects of the synthetic analogue of the toxin from the venom of the funnel-web spider Agenelopsis aperta (sFTX) on whole-cell Ba2+ currents through Ca2+ channels were studied in cultured bovine chromaffin cells. sFTX selectively and reversibly blocked a significant component (55 +/- 3%) of the whole-cell IBa. Effects of sFTX were additive to those of omega-conotoxin GVIA, a selective blocker of N-type Ca2+ channels, and those of furnidipine, a novel dihydropyridine L-type Ca2+ channel blocker. We conclude that the cultured bovine chromaffin cells, in addition to N- and L-type Ca2+ channels, possess a P-type component in their whole-cell currents through their Ca2+ channels.

Adrenal Medulla↗
PubMed1993

Administration of N omega-nitro-L-arginine ameliorates portal-systemic shunting in portal-hypertensive rats.

BACKGROUND: Nitric oxide, a vasodilator synthesized from L-arginine by vascular endothelial cells, may play a role in the development of portal-systemic collaterals. This study investigated the effect of long-term inhibition of NO secretion on portal systemic shunting. METHODS: Systemic and splanchnic hemodynamics and the degree of portal-systemic shunting were evaluated in partial portal vein-ligated rats after administration of placebo (0.9% saline) or N omega-nitro-L-arginine (NNA) (approximately 2 micrograms.kg-1 x min-1) intravenously for 6 days. RESULTS: NNA treatment induced increases in splanchnic arterial resistance (P < 0.001) and portal-collateral resistance (P < 0.05) and a decrease in portal venous inflow (P < 0.05). Portal pressure was not changed (NS). The splenic-systemic shunting was significantly decreased from 81% +/- 5% in the placebo-treated group to 69% +/- 4% in the NNA-treated group (P < 0.05), paralleled by an insignificant reduction in the mesenteric-systemic shunting (64% +/- 7% vs. 50% +/- 6%, NS). The attenuation of portal-systemic shunting by NNA was further shown by an increase in the vascular resistance of portal-systemic collateral venous bed using an in situ portal-systemic collateral perfusion model (1.27 +/- 0.05 vs. 1.07 +/- 0.03 cm H2O.mL-1 x min-1; P < 0.001). CONCLUSIONS: The results show that in portal hypertensive rats, NNA reduces portal-systemic shunting without reducing portal pressure, suggesting that NO plays a role in the collateralization of the portal system. In addition, high flow through the portal-collateral bed is probably an important driving force that is independent of portal hypertension for the development of portal-systemic shunting in portal-hypertensive rats.

Animals↗
PubMed1993

Octreotide ameliorates vasodilatation and Na+ retention in portal hypertensive rats.

BACKGROUND: Whether long-term octreotide treatment given to portal hypertensive rats could prevent or ameliorate peripheral vasodilatation and thereby modify sodium retention was investigated. METHODS: Starting at the time of partial portal vein ligation or sham operation, rats received a 4-day course of either octreotide (15 micrograms/kg in 5% dextrose in water) or placebo (5% dextrose in water) subcutaneously every 8 hours. RESULTS: In portal hypertensive rats, octreotide induced a 13% increase in mean arterial pressure (P < 0.01) and a 19% increase in total peripheral resistance (P < 0.01). Octreotide treatment induced a decrease in extracellular sodium space (22Na injection) (34.2 +/- 0.5 vs. 36.7 +/- 0.4 mL/100 g; P < 0.01) without changes in serum sodium level. In addition, octreotide treatment significantly reduced portal pressure as well as glucagon levels and plasma renin activity. In contrast, octreotide treatment had no effect on mean arterial pressure and extracellular sodium space in shamoperated rats. CONCLUSIONS: Long-term octreotide treatment ameliorated peripheral vasodilatation and sodium retention only in portal hypertensive rats. These findings suggest that in portal hypertension sodium retention can be modified by pharmacological agents that affect peripheral vasodilatation. The specificity of octreotide's effect sheds additional light into the vasodilatory syndrome associated with portal hypertension in liver diseases.

Animals↗
PubMed1993

R56865 inhibits catecholamine release from bovine chromaffin cells by blocking calcium channels.

1. The effects of R56865 (a new class of cardioprotective agent which prevents Na+ and Ca2+ overload in cardiac myocytes) on catecholamine release, whole-cell current through Ca2+ channels (IBa) and cytosolic Ca2+ concentrations, [Ca2+]i, have been studied in bovine chromaffin cells. 2. R56865 caused a time- and concentration-dependent blockade of catecholamine release from superfused cells stimulated intermittently with 5 s pulses of 59 mM K+. After 5 min superfusion, a 3 microM concentration inhibited secretion by 20%; the blockade increased gradually with perfusion time, to reach 85% after 40 min. The IC50 to block secretion after 5 min periods of exposure to increasing concentrations of R56865 was around 3.1 microM. The blocking effects of R56865 were reversible after 5-15 min wash out. In high Ca2+ solution (10 mM Ca2+), the degree of blockade of secretion diminished by 20% in comparison with 1 mM Ca2+. 3. In electroporated cells, R56865 (10 microM) did not modify the secretory response induced by the application of 10 microM free Ca2+. 4. R56865 blocked the peak IBa current in a concentration- and time-dependent manner; its IC50 was very similar to that obtained for secretion (3 microM). The compound not only reduced the size of the peak current but also promoted its inactivation; when the effects of R56865 were measured at the most inactivated part of the current, its IC50 was 1 microM. Both the inactivation and the reduction of the peak currents were reversible upon washing out the drug. 5. In fura-2-loaded single chromaffin cells the basal [Ca2+]i of around 100 nM was elevated to a peak of1.5 microM by the application of a 5 s pulse of 59 mM K+. R56865 (10 microM) did not affect the basal [Ca2+]but blocked by 90% the K+-evoked increase. This effect was fully reversible after 5-10 min of wash out.6. The results are compatible with the idea that R56865 blocks Ca2+ entry into K+-depolarized chromaffin cells by promoting the inactivation of voltage-dependent Ca2+ channels; this would lead to the limitation of the rise in [Ca2+]i and of the release of catecholamines. The restriction of catecholamine release may favour indirectly the known direct beneficial cardioprotective actions of R56865.

Animals↗
PubMed1993

N omega-nitro-L-arginine administration corrects peripheral vasodilation and systemic capillary hypotension and ameliorates plasma volume expansion and sodium retention in portal hypertensive rats.

In portal hypertensive states, peripheral vasodilation leads to sodium retention and plasma volume expansion. N omega-nitro-L-arginine, a specific biosynthesis inhibitor of the vasodilator nitric oxide, has been shown to acutely reverse peripheral vasodilation and the vascular hyporesponsiveness to endogenous and exogenous vasoconstrictors observed in portal hypertensive rats. This study investigated whether N omega-nitro-L-arginine treatment in portal hypertensive rats prevents peripheral vasodilation and therefore ameliorates plasma volume expansion and sodium retention. For 2 days before partial portal vein ligation or sham operation and then continuously for 4 days after the operation, animals received either placebo (0.9% saline) or N omega-nitro-L-arginine (approximately 2 micrograms/kg/min) intravenously through a subcutaneously implanted Alzet osmotic pump (model 2ML1; Alza, Palo Alto, CA). In portal hypertensive rats, N omega-nitro-L-arginine treatment significantly increased mean arterial pressure (placebo vs. N omega-nitro-L-arginine, 123 +/- 4 vs. 150 +/- 2 mm Hg, respectively; p < 0.001) and systemic vascular resistance (3.8 +/- 0.2 vs. 5.6 +/- 0.3 mm Hg/ml/min/100 gm body weight; p < 0.001), associated with a decrease in the cardiac index (33.5 +/- 1.0 vs. 27.0 +/- 1.1 ml/min/100 gm body weight; p < 0.001). N omega-nitro-L-arginine treatment also induced a decrease in plasma volume (4.6 +/- 0.1 vs. 4.1 +/- 0.1 ml/100 gm body weight; p < 0.001) and extracellular sodium space (39.4 +/- 0.7 vs. 37.4 +/- 0.4 ml/100 gm body weight; p < 0.05) without changes in serum sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Bacterial translocation in acute and chronic portal hypertension.

Patients with cirrhosis are predisposed to develop spontaneous bacteremias and peritonitis, mainly by enteric bacteria. Portal hypertension, by producing congestion and edema of the bowel wall, could increase the passage of bacteria from the intestinal lumen to regional lymph nodes to the systemic circulation or to both, a process termed bacterial translocation. The aim of this study was to investigate bacterial translocation at two stages of experimental portal hypertension: (a) acute (when shunting is minimal); and (b) chronic (when shunting is extensive and mimics the portal hypertension of cirrhosis). Rats were killed 2 days (acute) or 15 days (chronic) after partial portal vein ligation or control surgeries. Samples of mesenteric lymph nodes, blood, liver and spleen for standard bacteriological cultures and a fragment of ileum for histological examination were obtained. Two days after surgery, a significantly greater proportion of rats with acute portal hypertension (12 of 13 or 92%) had positive mesenteric lymph node cultures compared with both control groups: sham-operated (4 of 13 or 31%) and inferior vena cava-ligated (3 of 10 or 33%) animals (p < 0.01). However, 15 days after surgery no differences in translocation to mesenteric lymph nodes were found between rats with chronic portal hypertension (3 of 15 or 20%) and sham-operated controls (3 of 11 or 27%). In neither the acute nor the chronic rats were bacteria isolated from blood, spleen or liver. Rats with acute portal hypertension had significantly greater mesenteric inflammation than rats with chronic portal hypertension and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Cross-talk between M2 muscarinic and D1 dopamine receptors in the cat adrenal medulla.

In the study reported here we have reached two conclusions. First, the cat adrenal medulla chromaffin cell possesses a dopamine D1 receptor that seems to be coupled to an adenylyl cyclase. Second, this receptor regulates the muscarinic-mediated catecholamine release response through a negative feed-back loop which uses cyclic AMP as a second messenger. These conclusions are supported by the following findings: (i) SKF38393 (a selective D1 receptor agonist), but not quinpirole (a selective D2 agonist), inhibits the methacholine-mediated catecholamine release responses in a concentration-dependent manner (IC50 of around 1-2 microM). (ii) SCH23390 (a selective D1 antagonist), but not sulpiride (a selective D2 antagonist), reversed by 70% the inhibitory effects of SKF38393. (iii) Dibutyril cyclic AMP (500 microM) inhibited by 80% the secretory effects of methacholine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Temporal relationship of peripheral vasodilatation, plasma volume expansion and the hyperdynamic circulatory state in portal-hypertensive rats.

Peripheral vasodilatation and plasma volume expansion are required to generate the hyperdynamic circulatory state observed in portal hypertension. To determine which of these factors is the initial event and to assess their temporal relationship with the development of hyperdynamic circulation, we sequentially measured plasma volume (by 125I-albumin dilution), cardiac index (by thermodilution), mean arterial pressure (by catheterization), superior mesenteric and iliac arterial flows (by Doppler flowmetry) and calculated total and regional peripheral resistances in portal-hypertensive rats. Experimental groups were studied from day 1 through day 4 after partial portal-vein ligation (n = 110) or sham operation (n = 111). Decreased total peripheral resistance was detected within a day of portal-vein ligation (4.18 +/- 0.21 mm Hg.min.ml-1 x 100 gm vs. 5.19 +/- 0.16 mm Hg.min.ml-1 x 100 gm; p less than 0.01). Plasma volume increased significantly on day 2 (4.31 +/- 0.07 ml.100 gm-1 vs. 3.86 +/- 0.04 ml.100 gm-1; p less than 0.05). Cardiac index and regional blood flows increased in parallel with plasma volume elevation. On day 4, maximum values of plasma volume (4.49 +/- 0.08 ml.100 gm-1 vs. 3.73 +/- 0.03 ml.100 gm-1) coincided with fully developed hyperdynamic circulation, as shown by a significant elevation in cardiac index (32.3 +/- 0.6 ml.min-1 x 100 gm-1 vs. 25.5 +/- 1.2 ml.min-1 x 100 gm-1), iliac and mesenteric blood flow. On day 1, vasodilatation was present in the iliac arterial circulation. In contrast, the superior mesenteric artery vascular bed showed vasoconstriction in response to the protal outflow block.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Increased spontaneous and lymphokine-conditioned IgA and IgG synthesis by B cells from alcoholic cirrhotic patients.

Immunoglobulin secretion by B lymphocytes is a complex process in which lymphokines secreted by T lymphocytes play an important regulatory role. Increased serum levels of IgA and IgG have been characteristically detected in patients with alcoholic cirrhosis. We have studied the functional alterations of T and B lymphocytes implicated in the physiopathology of this common immunoglobulin abnormality. After activation with phytohemagglutinin, purified T cells from alcoholic cirrhotic patients showed significantly enhanced secretion of B-cell differentiation factors for IgG and IgA with respect to those secreted by T cells from healthy controls (p less than 0.05). Simultaneously, normal secretion of B-cell differentiation factor for IgM was demonstrated in T lymphocytes from these patients. The pattern of secretion of the lymphokines involved in the regulation of the B-cell differentiation pathway found in alcoholic cirrhotic patients was different from that of the primary biliary cirrhotic patients studied. Purified B cells from patients with alcoholic cirrhosis secreted significantly higher amounts of IgA and IgG than did those found in healthy controls, both spontaneously (p less than 0.05) and after sequential activation with immunoglobulin ligands (Staphylococcus aureus Cowan I) and a standard B-cell differentiation factor preparation (p less than 0.05). By contrast, the IgM secretion and regulatory pathway were normal in alcoholic cirrhotic patients. These results support a physiopathological explanation for the characteristic hyperimmunoglobulinemia found in patients with alcoholic cirrhosis.

Aged↗
PubMed1992

Deficient interleukin-2 responsiveness of T lymphocytes from patients with primary biliary cirrhosis.

There is increasing evidence that primary biliary cirrhosis is associated with an alteration of the immune system. Although the cause remains unknown, it has been suggested that the immune system of patients with primary biliary cirrhosis is involved in the pathogenesis of their disease. We have investigated the T-cell function in patients with primary biliary cirrhosis and have found defective phytohemagglutinin-induced T-cell mitogenesis. Likewise, their blastogenic response to CD3 monoclonal antibody was also depressed, although the DNA synthesis induced by stimulation with phorbol esters (12-O-tetradecanoil-phorbol-13-acetate) plus ionophore (ionomycin) was normal. These alterations could not be ascribed either to a decreased synthesis of interleukin-2 or to a defective expression of interleukin-2 receptor after cellular activation. Moreover, this defective proliferative response of T lymphocytes was observed even in the presence of saturating concentrations of exogenous interleukin-2. These results represent evidence of the deficiency in the interleukin-2-dependent pathway found in T lymphocytes from patients with primary biliary cirrhosis.

Cell Division↗
PubMed1992

The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in portal hypertensive rats.

This study examined whether an increased activity of the endothelium-derived relaxing factor, nitric oxide, may account for the hyporesponsiveness to vasoconstrictors in portal hypertension. We performed dose-response curves to methoxamine, an alpha-adrenoceptor agonist, with and without N omega-nitro-L-arginine, a specific inhibitor of nitric oxide synthesis, in experimental portal hypertension. Partial portal vein-ligated or sham-operated rats were pretreated with a continuous intravenous infusion of either N omega-nitro-L-arginine (50 micrograms.kg-1.min-1) or saline. Thirty minutes after starting the infusion of N omega-nitro-L-arginine or saline an infusion of methoxamine (10, 30 and 100 micrograms.kg-1.min-1) was added. Total peripheral resistance was calculated from mean arterial pressure and cardiac index. Repeated measurements of cardiac index were performed by a thermodilution technique. In portal vein-ligated rats pretreated with saline, the increase in total peripheral resistance after methoxamine infusion was significantly less than that of sham-operated rats (0.2 +/- 0.1 vs. 1.0 +/- 0.3, 0.6 +/- 0.1 vs. 1.6 +/- 0.3 and 3.7 +/- 0.5 vs. 6.1 +/- 0.7 mm Hg.ml-1.min.100 gm, p less than 0.05, methoxamine 10, 30 and 100 micrograms.kg-1.min-1, respectively). In the presence of N omega-nitro-L-arginine, the change in total peripheral resistance after methoxamine infusion was similar in both groups (p greater than 0.05). In conclusion, this study demonstrates that a vascular hyporesponsiveness to methoxamine is present in portal vein-ligated rats and that this hyporesponsiveness is reversed by blockade of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Vasodilatation and sodium retention in prehepatic portal hypertension.

Sodium retention and peripheral vasodilatation are common consequences of portal hypertension secondary to cirrhosis. Although peripheral vasodilatation has been extensively documented in prehepatic portal hypertension, it is not known whether sodium retention is also a feature of this entity. The aim of this study in portal vein-constricted rats was to evaluate (a) whether sodium retention is a feature of prehepatic portal hypertension and (b) if sodium retention is present in this model, what its temporal relationship with peripheral vasodilatation might be. It was proposed that an understanding of the temporal interplay between peripheral vasodilatation and sodium retention could shed light on the current theories of sodium retention in portal hypertension. Rats were studied 1, 2, 3, and 4 days after partial portal vein ligation (n = 80) or sham operation (n = 63). Sodium retention was evaluated by changes in the size of the sodium space measured by the volume of distribution of 22Na. Systemic vascular resistance was calculated from mean arterial pressure (measured by arterial catheterization) and cardiac index (measured by thermodilution). A decrease in systemic vascular resistance was already observed on day 1 after constriction of the portal vein (4.2 +/- 0.2 vs. 5.2 +/- 6.1 mm Hg.min.mL-1.100 g; P less than 0.01). However, an expansion of the sodium space, which indicates sodium retention, was not observed until day 2 after induction of portal hypertension (37.1 +/- 0.8 vs. 32.6 +/- 0.7 mL.100 g-1; P less than 0.01). Therefore, sodium retention should be considered along with peripheral vasodilatation among the characteristic features of prehepatic portal hypertension. Because the reduction in systemic vascular resistance preceded the expansion of the sodium space by at least 24 hours, the finding of this study indicates that sodium retention follows peripheral vasodilatation.

Animals↗