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1. |
Short- and Long-Term Treatment with Indometacin Causes Renal Phospholipid Alteration: A Possible Explanation for Indometacin Nephrotoxicity |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 341-348
Maria del Carmen Fernández-Tomé,
Norma B. Sterin-Speziale,
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摘要:
Phospholipid content was studied in kidneys from rats treated with indometacin. Short-term treatment was performed by using low (1 and 5 mg/kg/day) and high (10 and 50 mg/kg/day) doses of indometacin. Long-term treatment was achieved by using only low doses of indometacin. Short-term treatment at low doses did not result in any change in the phospholipid content. In rats administered higher concentrations, indometacin caused a marked increase in all papillary phospholipid contents, but no effect was observed in the medulla, and an increase in sphingomyelin and phosphatidylethanolamine was observed in the cortex. Long-term treatment with administration of 1 mg/kg/day of indometacin led to an increase in all papillary phospholipids from the 2nd week of treatment. Medullary phospholipids also increased, but no changes were observed in cortical phospholipids. These results show that indometacin causes phospholipid accumulation in rat kidney and that the papilla is the most sensitive renal tissue.
ISSN:0031-7012
DOI:10.1159/000139199
出版商:S. Karger AG
年代:1994
数据来源: Karger
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2. |
Effects of Wortmannin on Alpha-1/Alpha-2 Adrenergic Receptor-Mediated Contractile Responses in Rabbit Vascular Tissues |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 349-359
Viviana I. Waen-Safranchik,
Richard C. Deth,
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摘要:
The inhibitory effect of wortmannin (WO), a fungus-derived protein kinase inhibitor, was assessed on contractile responses elicited by phenylephrine-induced α1-(α1R) and UK 14304-induced α1-adrenergic receptor (α1R) stimulation in the rabbit aorta and saphenous vein, respectively. In agonist dose-response studies, WO caused a noncompetitive inhibition of both α1R and α1R responses, but was more potent against α1R. Maximally effective single-dose responses at both receptors were less sensitive to WO. The initial α1 contractile response, associated with intracellular Ca2+ release and myosin light chain kinase activation, was relatively insensitive to WO, while the Ca2+ influx-dependent tonic contraction was more sensitive. Contractions induced by high K+ buffer were relatively insensitive to WO in both the aorta and saphenous vein. These results indicate that WO inhibits receptor-initiated Ca2+ influx-dependent contractile responses such as those caused by α1R stimulation and the sustained phase of α1R stimulation more readily than Ca2+ release-dependent
ISSN:0031-7012
DOI:10.1159/000139200
出版商:S. Karger AG
年代:1994
数据来源: Karger
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3. |
Different Effects of Harmine on Plasma Concentrations ofL-Dopa and on Cerebral Dopamine Metabolism in Rabbits and Rats |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 360-366
A. Meneguz,
P. Betto,
G. Ricciarello,
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摘要:
The effects of short-term intravenous administration of harmine, a monoamine oxidase inhibitor, on the plasma concentrations of L-Dopa and on dopamine levels in the brain striata of rats and rabbits after L-Dopa administration were studied. Harmine affects the L-Dopa plasma concentrations in rabbits but not in rats: in fact in the former species the area under the concentration-time curve observed after administration of L-Dopa alone increased significantly when animals were pre-treated with harmine. Dopamine striatal levels increased in concert with plasma L-Dopa concentrations after administration of L-Dopa in rats and rabbits. However pretreatment with harmine resulted in a significant increase of dopamine levels in the brain striata of rabbits only. These results suggest that harmine or one of its metabolites affect the brain dopamine system not merely as a type A monoamine oxidase inhibitor but with a modulatory effect, without a precise indication of site or mode of action of harmine.
ISSN:0031-7012
DOI:10.1159/000139201
出版商:S. Karger AG
年代:1994
数据来源: Karger
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4. |
Effects of Inhibition of Nitric Oxide Synthase on Blood-Brain Barrier Transport in Focal Cerebral Ischemia |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 367-373
Oak Za Chi,
Hwu Meei Wei,
Arabinda K. Sinha,
Harvey R. Weiss,
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摘要:
This study was performed to determine whether nitric oxide (NO) alters the transport of small hydrophilic molecules across the blood-brain barrier in focal cerebral ischemia by administering an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and by measuring the blood-brain barrier transfer coefficient (Ki) of 14C-α-aminoisobutyric acid (14C-AIB) in the rats with middle cerebral artery occluded under isoflurane anesthesia. L-NAME increased the mean arterial blood pressure from 91 ± 9 to 134 ± 13 mm Hg. The Ki of the ischemic cortex (ICO) was 26% higher than that of the contralateral cortex (CCO) in the control animals without the L-NAME treatment. However, in the L-NAME-treated animals, Ki was 33% lower in the ICO than in the CCO. The Ki of ICO in the L-NAME group was significantly lower (-54%) than that of the control group. L-NAME did not affect Ki significantly in the nonischemic brain regions. Our data demonstrate that focal ischemia increased Ki of 14C-AIB, but L-NAME significantly decreased the Ki in the focal ischemic area of the brain without causing significant changes in the nonischemic tissue. Our results suggest that NO may participate in increasing transport of small hydrophilic molecules across the blood-brain barrier in focal ische
ISSN:0031-7012
DOI:10.1159/000139202
出版商:S. Karger AG
年代:1994
数据来源: Karger
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5. |
Effect of Amphiphiles on Nitric Oxide Synthase in Endothelial Cells |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 374-379
R. Dudek,
A. Conforto,
V. Pinto,
R.J. Bing,
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摘要:
Amphiphiles are known to modulate the activity of ATPase, phopholipase A2, adenylate and guanylate cyclase amongst others and relax vascular smooth muscle. The effect of two amphiphiles, lysophosphatidylcholine (LPC) and digitonin on the activity of nitric oxide synthase (NOS), as measured by conversion of radiolabeled L-arginine to L-citrulline, has been studied. Neither digitonin (0.01 mmol/l) nor LPC (0.01 mmol/l) influenced NOS activity in endothelial cell homogenates. Digitonin but not LPC stimulated NOS in intact endothelial cells. NOS activity was markedly inhibited by L- but not by D-ω-nitroarginine (D-NNA, 0.1 mmol/l). L-NNA or D-NNA data demonstrate no effect of amphiphiles on isolated NOS. NOS activation may occur as a result of detergent action on the membrane
ISSN:0031-7012
DOI:10.1159/000139203
出版商:S. Karger AG
年代:1994
数据来源: Karger
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6. |
What Is the Most Accurate Way to Study the Active Properties of Bladder Smooth Muscle? |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 380-384
Stephen A. Zderic,
Guo-Hua Liu,
Jean P. Haab,
Frederick C. Monson,
Chiaoliang Gong,
Robert M. Levin,
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摘要:
There is often disagreement over the optimal method by which to study the active properties of smooth muscle. While some favor setting smooth muscle strips at a resting or passive tension of 1 g, others have argued in favor of determining the Lo or optimal length for maximal force generation for each individual strip. Setting each strip to its individual Lo is tedious, especially if one is dealing with multiple strips during one experiment. Is it possible to study smooth muscle strips at an average length at which most strips of similar dimensions exhibit their maximal force, and if this method is used to what extent does it underestimate the maximal force generated? When comparing bladder smooth muscle strips 1 cm long from pregnant versus virginal rabbits, the average length at which maximal force was generated was 2.41 and 2.45 cm, respectively (p = n.s.). Studying all strips at a length of 2.5 cm (2.5 × the slack length) would have resulted in a 10% underestimate of the maximal force within each group (p = n.s.). We conclude that comparative bladder smooth muscle strip studies can be accurately carried out at an average fixed length provided that preliminary studies are done to determine the length-tension relationships for the specific experimental situation
ISSN:0031-7012
DOI:10.1159/000139204
出版商:S. Karger AG
年代:1994
数据来源: Karger
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7. |
A Potent Antioxidant, SB209995, Inhibits Oxygen-Radical-Mediated Lipid Peroxidation and Cytotoxicity |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 385-391
Ron Feuerstein,
Tian-Li Yue,
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摘要:
The antioxidant activity of SB209995, a metabolite of carvedilol in human, was studied and compared with its parent compound, carvedilol. SB209995 or carvedilol inhibited iron-catalyzed lipid peroxidation assessed as thiobarbituric acid-reactive substance generated in brain homogenate with IC50s of 0.30 and 8.1 µmol/l, respectively. The oxidation of low-density lipoprotein (LDL) by macrophages or that initiated by Cu2+ ions was inhibited by SB209995 with IC50s of 59 nmol/l and 1.7 µmol/l, respectively. Under the same conditions, the IC50s of carvedilol were 3.8 and 17.1 µmol/l, respectively. Furthermore, SB209995 protected cultured endothelial cells against hydroxyl radical (OH) or superoxide (O–2)mediated lipid peroxidation and cytotoxicity, assessed as lactate dehydrogenase release and cell death. The results indicate that SB209995 is a more potent antioxidant than carvedilol and may contribute to the therapeutic effects of carved
ISSN:0031-7012
DOI:10.1159/000139205
出版商:S. Karger AG
年代:1994
数据来源: Karger
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8. |
Protective Effect of Ternatin, a Flavonoid Isolated fromEgletes viscosa less.,in Experimental Liver Injury |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 392-397
V.S.N. Rao,
E.G. Figueiredo,
C.L. Melo,
G.S.B. Viana,
D.B. Menezes,
M.S.F. Matos,
E.R. Silveira,
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摘要:
The effect of ternatin, a tetramethoxyflavone from Egletes viscosa Less., on liver injury induced by carbon tetrachloride (CCI4) was investigated in rats. Twenty-four hours following CCI4 insult (2.5 ml/kg s.c), changes in the serum enzymes, alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, as well as liver cell histology were used as indices of hepatic dysfunction. The results show that ternatin (30 mg/kg i.p daily for 5 consecutive days) causes marked inhibition of CCLl4-induced serum enzymes and morbid histologic changes. The observation suggests that ternatin possesses anti-hepatotoxic activity
ISSN:0031-7012
DOI:10.1159/000139206
出版商:S. Karger AG
年代:1994
数据来源: Karger
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9. |
Author Index, Vol. 48, 1994 |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 398-399
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ISSN:0031-7012
DOI:10.1159/000139207
出版商:S. Karger AG
年代:1994
数据来源: Karger
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10. |
Subject Index, Vol. 48, 1994 |
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Pharmacology,
Volume 48,
Issue 6,
1994,
Page 400-404
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ISSN:0031-7012
DOI:10.1159/000139208
出版商:S. Karger AG
年代:1994
数据来源: Karger
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