bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Endogenous Nitric Oxide Synthesis Potentiates the Effects of Sodium Nitroprusside but Not of Adenosine in Experimental Pulmonary Hypertension
Authors: Wall Michael H. , Patterson Kenneth W. , Kavanagh Brian P. , Pearl RonaldG. 
Published: April 2003

This study examined the systemic and pulmonary vasodilator effects of sodium nitroprusside (SNP) and adenosine during experimental pulmonary hypertension with and without inhibition of endogenous NO synthesis. Male New Zealand White rabbits were anesthetized and mechanically ventilated. The NO synthesis inhibitor N<sup>G</sup>-nitro-L-arginine methyl ester (L-NAME) was administered to 15 of the 28 rabbits. Pulmonary hypertension was then produced in all rabbits by U46619, a thromboxane A<sub>2</sub> mimetic. SNP was infused in 14 rabbits (7 L-NAME, 7 control) at doses of 0.5–20 µg/kg/min; adenosine was infused in the other 14 rabbits (8 L- NAME, 6 control) at doses of 12.5–300 µg/kg/min. The U46619 dose required to produce pulmonary hypertension was significantly lower in the L-NAME group. SNP dose-dependently decreased pulmonary (Ppa) and systemic (Psa) artery pressures and systemic vascular resistance (SVR). Both Ppa and Psa were decreased more with SNP in the L-NAME than in the no L-NAME group. The SNP ED<sub>50</sub> for the decrease in PVR was almost threefold lower in the L-NAME group. Adenosine dose-dependently decreased Ppa, Psa, PVR and SVR. The adenosine ED<sub>50</sub> for the decreases in PVR and SVR were similar in the L-NAME group and the control group. We conclude that inhibition of endogenous NO synthesis shifts the dose-response curves for both the pulmonary and systemic vasodilator effects to the left for the nitrovasodilator SNP but not for the non-nitrovasodilator adenosine.
Acute and Chronic Citalopram Treatment Differently Modulates Rat Exploratory Behavior in the Exploration Box Test: No Evidence for Increased Anxiety or Changes in the [<sup>3</sup>H]Raclopride Binding
Authors: Matto Vallo , Allikmets Lembit 
Published: April 2003

The effect of acute and chronic desipramine (10 mg/kg) and citalopram (10 mg/kg) treatment on rat exploratory behavior in the recently developed exploration box test was studied on 5 consecutive days. Acute desipramine but not citalopram treatment decreased the time spent exploring, the number of line crossings, rears, investigative approaches, entries into the large arena, and sum of exploratory events. After 3 weeks of pretreatment, both desipramine and citalopram attenuated rat exploratory behavior, whereas the number of entries into the large arena was unchanged. In the open field test, acute desipramine or citalopram treatment (5, 10, 15 mg/kg) attenuated rat exploratory behavior in a dose-dependent manner. In the subsequent rota-rod test, neither desipramine nor citalopram treatment (0–20 mg/kg) impaired motor performance capacity. In an additional experiment, [<sup>3</sup>H]raclopride binding was unchanged after single as well as 3 weeks of desipramine or citalopram treatment in the rat brain neostriatum. Our experiments demonstrate that acute citalopram treatment in the open field test and chronic citalopram treatment in the exploration box test attenuate rat exploratory behavior, but these effects may not be implicated with enhanced anxiety or changed dopamine D<sub>2</sub> receptor characteristics.
Inhaled Nitric Oxide Potentiates Actions of Adenosine but Not of Sodium Nitroprusside in Experimental Pulmonary Hypertension
Authors: Patterson Kenneth W. , Deb Bhaskar , Kavanagh Brian P. , Pearl RonaldG. 
Published: April 2003

Inhaled nitric oxide (NO), a selective pulmonary vasodilator, increases intracellular cyclic guanosine monophosphate. In contrast, adenosine, another selective pulmonary vasodilator, increases intracellular cyclic adenosine monophosphate. There has been only limited study on effects of inhaled NO combined with other pulmonary vasodilators. The current study examined the hypothesis that inhaled NO would potentiate in vivo pulmonary vasodilator effects of adenosine, but not those of sodium nitroprusside (SNP). Like inhaled NO, SNP acts via cyclic guanosine monophosphate. Rabbits were anesthetized and mechanically ventilated. The NO synthesis inhibitor N<sup>G</sup>-nitro-L-arginine methyl ester was administered. U46619, a thromboxane A<sub>2</sub> mimetic, was infused to produce pulmonary hypertension. Rabbits then received either SNP at doses of 0.5, 1, 2, 4, 8, 16, and 32 µg/kg/min or adenosine at doses of 12.5, 25, 50, 100, 150, and 300 µg/kg/min. Hemodynamic measurements were obtained with or without inhaled NO (40 ppm) at each dose of SNP or adenosine. During U46619-induced pulmonary hypertension, inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance. Adenosine and SNP produced dose-related decreases in pulmonary artery pressure and pulmonary vascular resistance and increases in cardiac output. Inhaled NO decreased pulmonary artery pressure and pulmonary vascular resistance at all doses of adenosine, but had no significant pulmonary vasodilator effects at doses of SNP >0.5 µg/kg/min. We conclude that inhaled NO does not produce additional pulmonary vasodilation over that achieved at higher doses of SNP, but does produce additional vasodilation when combined with a vasodilator having different mechanisms of action. Since both inhaled NO and adenosine produce selective pulmonary vasodilation, such combination therapy may be effective in patients with pulmonary hypertension.
Use of Diffusion-Weighted MRI and Neurological Deficit Scores to Demonstrate Beneficial Effects of Isradipine in a Rat Model of Focal Ischemia
Authors: Chandra Sudeep , White Ray F. , Everding Daryl , Feuerstein Giora Z. , Coatney Robert W. , Sarkar Susanta K. , Barone Frank C. 
Published: April 2003

The neuroprotective effects of isradipine, a 2,4-dihydropyridine calcium channel blocker, has been well studied in the rat model of focal ischemia (induced by middle cerebral artery occlusion, MCAO). The present study was designed to evaluate whether isradipine pretreatment caused early (0–3 h after stroke) ischemic changes in diffusion- weighted magnetic resonance imaging (DWI) and if such changes were predictive of previously documented protection in brain infarction. An initial dose-response study using neurological deficit scores and estimates of protection from brain infarction (by histology) showed that isradipine reduced cortical infarctions compared to vehicle-treated animals at most doses (between 1.25 and 5 mg/kg/day s.c. for 6 days) with the best results obtained at 5 mg/kg/day, where a 78.5% reduction was observed. This dose was utilized to perform the DWI study. Early quantitative estimates of infarct size, as measured by DWI at 1, 2 and 3 h after MCAO, were similar to those obtained with late histology at 24 h. These data indicate that in pretreatment protocols, DWI can be used to quantitatively predict areas at risk of permanent damage. This work also demonstrates that neurological deficits, developing from the damaged forebrain following focal stroke, may provide an index of isradipine’s neuroprotective activity.
Influence of L-365,260, a CCK-B/Gastrin Receptor Antagonist, on Tetragastrin- Stimulated Mucin Metabolism in Rat Gastric Mucosa
Authors: Komuro Yuichi , Ichikawa Takafumi , Ishihara Kazuhiko , Saigenji Katsunori , Hotta Kyoko 
Published: April 2003

The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 μg/kg s.c.)-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 μg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70–80% of tetragastrin) and the mucus gel (45–70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1–10 μmol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 μg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.
In vivo Receptor Occupancy and Plasma Concentration of Pranidipine, a Potent and Long-Acting Dihydropyridine Calcium Antagonist
Authors: Yamada Shizuo , Uchida Shinya , Urayama Akihiko , Kimura Ryohei 
Published: April 2003

The occupancy of 1,4-dihydropyridine (DHP) receptors by pranidipine was characterized in tissues of spontaneously hypertensive rats (SHR). Oral administration of pranidipine (1 and 3 mg/kg) in SHR produced significant (26–67%) decreases in the number of specific (+)-[<sup>3</sup>H]PN 200-110 binding sites (B<sub>max</sub>) with 2- to 4-fold increases in the apparent dissociation constant (K<sub>d</sub>) in myocardial tissues at 1, 3 and 6 h later. In these rats, there was a reduction (16–37%) of B<sub>max</sub> in cerebral cortical (+)-[<sup>3</sup>H]PN 200-110 binding. Occupancy of myocardial DHP receptors after oral administration of pranidipine correlated well with its plasma concentration. Oral administration of nifedipine (10 mg/kg) in SHR caused significant increase in K<sub>d</sub> values for (+)-[<sup>3</sup>H]PN 200-110 binding in myocardium and cerebral cortex at 1 h later. In vivo specific (+)-[<sup>3</sup>H]PN 200-110 binding in particulate fractions of SHR aorta was markedly (59–78%) reduced at 1, 3 and 12 h after oral administration of pranidipine (3 mg/kg), while myocardial (+)-[<sup>3</sup>H]PN 200-110 binding was decreased by 46–48% at 1 and 3 h later. In these rats, there was a significant decrease (34%) in cerebral cortical (+)-[<sup>3</sup>H]PN 200-110 binding at 3 h later. In contrast, nifedipine administration produced a similar degree of reduction (71–84%) of in vivo (+)-[<sup>3</sup>H]PN 200-110 binding in the myocardium, aorta and cerebral cortex. It is concluded that pranidipine may exert more selective and sustained occupation in vivo of DHP receptors in vascular tissues of SHR than in myocardial and brain tissues.
Sustaining Effects of Bopindolol on Inhibitory Chronotropic Actions in Guinea Pig Atria
Authors: Hattori Kaoru , Suzuki Jun , Hosohata Yoshiaki , Ohnuki Toshio , Nakamura Takashi , Watanabe Kenichi , Muramatsu Ikunobu , Nagatomo Takafumi 
Published: April 2003

The dissociating and/or residual inhibitory effects of bopindolol from β-adrenoceptors (ARs) of atria strips pretreated with this drug and washed out with buffers on isoprenaline-induced chronotropic actions were determined. The effects of this drug were compared with those of its active metabolite 18-502, propranolol, and pindolol. Our results are as follows: (1) Lower concentrations of bopindolol (10<sup>–9</sup> and 10<sup>–8</sup> mol/l) and the active metabolite 18-502 (10<sup>–9</sup> mol/l), propranolol (10<sup>–8</sup> and 10<sup>–6</sup> mol/l) and pindolol (10<sup>–8</sup> mol/l) produced rightward shifts of concentration-response curves of isoprenaline. (2) Higher concentrations of bopindolol (10<sup>–7</sup> mol/l) and 18-502 (10<sup>–8</sup> and 10<sup>–7</sup> mol/l) produced a reduced maximum response by isoprenaline. (3) Bopindolol (10<sup>–9</sup>–10<sup>–7</sup> mol/l), 18-502 (10<sup>–9</sup>–10<sup>–7</sup> mol/l) and propranolol (10<sup>–7</sup> and 10<sup>–6</sup> mol/l) did not recover to control levels at 180 min even after washout with buffers. In conclusion, bopindolol and 18-502 may slowly dissociate and act as noncompetitive β-antagonists rather than readily reversible β-AR antagonists. These effects may differ from those of propranolol and pindolol, although propranolol did not recover to control levels after washout with buffer.
Antiarrhythmic Effect of Magnolol and Honokiol during Acute Phase of Coronary Occlusion in Anesthetized Rats: Influence of <i>L</i>-NAME and Aspirin
Authors: Tsai Shen Kou , Huang Cheng Hsiung , Huang Shiang Suo , Hung Li Man , Hong Chuang Ye 
Published: April 2003

This study was designed to evaluate the in vivo effect of magnolol and honokiol on the acute phase of coronary ligation in the presence of nitric oxide inhibitor (<i>L</i>-NAME) or cyclooxygenase inhibitor (aspirin). After Sprague-Dawley rats were anesthetized with urethane, the changes of ventricular arrhythmia induced by coronary ligation for 30 min were determined with or without pretreatment with study medications. The incidence and duration of ventricular arrhythmia were significantly reduced after intravenous pretreatment (15 min before coronary ligation) with 10<sup>–7</sup> g/kg magnolol or 10<sup>–7</sup> g/kg honokiol. However, the antiarrhythmic effect of magnolol or honokiol could be abolished with the pretreatment of 1 mg/kg <i>L</i>-NAME, but not with pretreatment of 100 mg/kg aspirin. The abolishment of the myocardial beneficial effect of magnolol and honokiol by <i>L</i>-NAME, instead of aspirin, suggests an involvement of an increased nitric oxide synthesis in the protection offered by magnolol and honokiol against arrhythmia during myocardial ischemia.
Comparison of the Effects of Selective III, IV and Nonselective Phosphodiesterase Inhibitors on Isolated Tracheal Preparations in Streptozotocin-Diabetic Rats
Authors: Usta Coşkun , Şadan Gülay 
Published: April 2003

The aim of the present study was to investigate the relaxant effects of selective III, IV and nonselective phosphodiesterase inhibitors, e.g. amrinone, rolipram and theophylline, respectively, on isolated tracheal preparations in streptozotocin (STZ)-diabetic rats. Six weeks before the experiments, the rats to be made diabetic were anesthetized with diethyl ether and diabetes was then induced by a single intravenous injection of STZ (65 mg kg<sup>–1</sup>) via the tail vein. All drugs produced concentration-dependent relaxations of tracheal preparations precontracted with 10<sup>–6</sup> mol/l carbachol. The responses of phosphodiesterase inhibitors were marked in the diabetic groups compared to the control group, but it was found that only amrinone responses are significantly higher in the diabetic groups.
Effect of Antioxidants on Pyrogallol-Induced Delay in Gastric Emptying in Rats
Authors: Sharma Monisha , Rai Kamala , Sharma Shyam S. , Gupta Yogendra K. 
Published: April 2003

The effect of a free radical generator pyrogallol on gastric emptying was studied in rats. Pyrogallol at doses of 25, 50, 100 and 150 mg/kg (i.p.) produced dose-dependent inhibition of gastric emptying. Pretreatment with vitamin C (100 and 500 mg/kg, p.o.), and vitamin E (100 and 500 mg/kg, p.o.) significantly reversed the inhibition in gastric emptying caused by pyrogallol 100 mg/kg. However, the combination of vitamin C and vitamin E (100 mg/kg) produced synergistic effect. Glutathione (100 mg/kg i.v.) 5-min pretreatment also reversed the inhibition of gastric emptying caused by pyrogallol 100 mg/kg. Ondansetron (3 mg/kg, p.o.) significantly reversed the pyrogallol effect. The effect of pyrogallol on malondialdehyde (MDA) levels and 5-HT levels in the stomach tissue was also studied. Pyrogallol at a dose of 100 mg/kg, i.p., significantly increased MDA levels and 5-HT levels in the stomach. Pretreatment with a combination of vitamin C and vitamin E (100 mg/kg, p.o.) and glutathione (100 mg/kg, i.v.) significantly ameliorated the rise in stomach tissue MDA caused by pyrogallol but had no significant effect on the rise in 5-HT levels caused by pyrogallol. The effect of different doses of 5-HT on gastric emptying was also studied. 5-HT had a differential effect on gastric emptying. The low and high doses (0.1, 0.3 and 30 mg/kg, i.p.) significantly inhibited the gastric emptying while doses ranging from 1 to 10 mg/kg, i.p., had no significant effect on the gastric emptying. The pretreatment with antioxidants, combination of vitamin C and vitamin E (100 mg/kg each, p.o.) and glutathione (100 mg/kg, i.v.) had no effect on the 5-HT (0.3 mg/kg, i.p.)-induced delay in gastric emptying. The result indicate the role of free radicals gastric emptying, and antioxidants may be of potential therapeutic value in disease conditions where free radicals are known to be released and the gastrointestinal effects are observed as symptoms or side effects of drug therapy.
Influence of Polyunsaturated Fatty Acids on Vasoconstrictions Induced by 8-iso-PGF<sub>2α</sub> and 8-iso-PGE<sub>2</sub>
Authors: Sametz Wolfgang , Jeschek Mirjam , Juan Heinz , Wintersteiger Reinhold 
Published: April 2003

8-iso-PGF<sub>2α</sub> and 8-iso-PGE<sub>2</sub>, which are released in vivo by free radical catalyzed peroxidation of arachidonic acid, are equipotent vasoconstrictors in vivo and in vitro. It is assumed that they exert this effect via activation of the thromboxane A<sub>2</sub> (TP) receptor or a TP-receptor-like isoprostane receptor. Increased levels of 8-iso-PGF<sub>2α</sub> have been detected in human cardiovascular diseases. It has been found that polyunsaturated fatty acids (PUFAs) have many beneficial effects in cardiovascular diseases, including antivasoconstrictor actions. Therefore, we investigated the influence of perfusions with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and dihomo-γ-linolenic acid (DGLA) at final concentrations of 3 and 30 μmol/l on vasoconstriction induced by 8-iso-PGF<sub>2α</sub>, 8-iso-PGE<sub>2</sub> and the thromboxane A<sub>2</sub> mimetic U 46619 in the vasculature of the isolated perfused rabbit ear. Additionally, the effect of indomethacin (final concentration 3 μmol/l) on the effects of the PUFAs was investigated. Our results show that the PUFAs at a concentration of 30 μmol/l caused a significant inhibition of the vasoconstrictions induced by 8-iso-PGF<sub>2α</sub>, 8-iso-PGE<sub>2</sub> and U 46619. Furthermore, it can be assumed that a part of the inhibitory effect of DGLA is due to the effect of a cyclooxygenase product, probably PGE<sub>1</sub>, because indomethacin reduced the inhibitory effect of DGLA.
Effects of Centrally Applied Somatostatin on Pituitary Adrenocorticotropes in Female Rats
Authors: Starčević Vesna , Milošević Verica , Brkić Branislava , Severs Walter B. 
Published: April 2003

Effects of intracerebroventricular (i.c.v.) application of somatostatin (SRIH-14 or SRIH-28) on growth and function of pituitary adrenocorticotropes (ACTH cells) were examined in adult female Wistar rats. Animals were subjected to i.c.v. administration of three 1-μg doses of SRIH-14 or SRIH-28 dissolved in 5 μl saline every second day. Controls were treated in the same way with the same volume of saline only. ACTH-producing cells were studied using the peroxidase-antiperoxidase (PAP) immunohistochemical procedure; blood samples were collected for hormone analyses 5 days after the last injection. SRIH-28 treatment decreased (p < 0.05) all morphometric parameters compared to control rats. Volume of ACTH cells decreased by 10%, nuclei by 36% and volume density by 13%. No significant changes (p > 0.05) in these parameters occurred after SRIH-14 treatment. Plasma concentration of ACTH in SRIH-28-treated rats was significantly lower (p < 0.05) than in control rats by 35%. In SRIH-14-treated rats, plasma concentration of ACTH was slightly, but not significantly (p > 0.05) increased by 13% compared to saline treatment. These observations suggest that centrally administered somatostatin-28, but not somatostatin-14, is specifically involved in the control of growth and secretory activity of ACTH cells in female rats. Thus, selective pharmacological manipulation of SRIH-28 receptors reached from CSF may affect ACTH activity without altering actions usually attributed to receptors sensitive to SRIF-14.
Effect of FRG-8813, a New-Type Histamine H<sub>2</sub>-Receptor Antagonist, on the Recurrence of Gastric Ulcer after Healing by Drug Treatment in Rats
Authors: Ajioka Hirofusa , Miyake Hidekazu , Matsuura Naosuke 
Published: April 2003

We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (±)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H<sub>2</sub>-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p.o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days’ administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy.
Role of Nitric Oxide in Gastric Injury Induced by Hemorrhagic Shock in Rats
Authors: Denizbaşı Arzu , Yegen Cumhur , Öztürk Melek , Yegen Berrak 
Published: April 2003

The aim of this study was to investigate the effect of nitric oxide (NO) on the gastric injury induced by hemorrhagic shock. Hemorrhagic shock was created by withdrawing 3 ml blood/200 g body weight of the rats. Before the hemorrhage, N<sup>G</sup>-nitro-<i>L</i>-arginine methyl ester (<i>L</i>-NAME, 10 mg/kg i.v. bolus), <i>D</i>-NAME (10 mg/kg i.v. bolus), or <i>L</i>-arginine (100 mg/kg i.v. bolus and 10 mg/kg/min infusion) + <i>L</i>-NAME were administered. At the end of the 1-hour hypovolemic shock period, histological analysis, gastric ulcer index, gastric myeloperoxidase (MPO) activity, and gastric protein oxidation (PO) levels were determined. In histological analysis a destructive effect of <i>L</i>-NAME (NO synthase inhibitor) was demonstrated. <i>L</i>-NAME treatment increased gastric MPO activity, <i>L</i>-arginine reversed this effect and <i>D</i>-NAME had no effect. Tissue PO activity was found to be increased in <i>L</i>-NAME-treated rats; <i>L</i>-arginine treatment reversed this activity. It is concluded that gastric barrier function is altered after hemorrhagic shock, and <i>L</i>-arginine (NO precursor) can prevent mucosal injury in the stomach. This effect of NO may be on gastric blood flow and can be mediated by tissue neutrophils.