摘要:

Adenosine uptake by cultured rabbit coronary microvascular endothelial cells was studied. Radiolabeled [2-3H]-adenosine, present initially in the extracellular space at 10–6 mol/l, was incorporated into the cell cultures at a steady rate during 30 s–3 h incubations. Incorporated 3H was found mostly (83%) in adenine nucleotides. Incorporation of [3H]-adenosine was attenuated by an adenosine deaminase inhibitor (EHNA) but only at adenosine concentrations of 10–5 mol/l or higher. Adenosine transport inhibitors (dipyridamole, nitrobenzylthioinosine) attenuated 3H incorporation. Adenosine uptake was also diminished by certain structural analogues of adenosine (e.g., 2-chloroadenosine), by several alkylxanthine drugs (theophylline, isobutylmethylxanthine, enprofylline and 8-phenyltheophylline), and by certain calcium antagonists (verapamil, nifedipine and trifluoperazine). The mechanisms of actions of these agents on adenosine uptake do not appear to be related to phosphodiesterase inhibition, adenosine receptor antagonism or calcium antagonism. The effects of varying adenosine metabolism may contribute to the pharmacologic actions of these a

ISSN:0031-7012    

DOI:10.1159/000138290

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The purpose of the present study was to determine if 8-bromo cyclic guanosine monophosphate (cGMP) mimics the actions of nitroglycerin in inhibiting α1-versus α2-mediated constrictor responses in vitro using rings prepared from isolated canine saphenous vein. Contractions were produced by phenylephrine, a selective αi-adrenoceptor agonist and B-HT 920, a selective α1-adrenoceptor agonist. The inhibitory effects of nitroglycerin and 8-bromo cGMP on contractions produced by submaximal concentrations (EC75) of phenylephrine and B-HT 920 were determined. 8-Bromo cGMP like nitroglycerin produced a selective antagonism of α2-adrenoceptor-mediated responses and had minimal effects on α1-adrenoceptor-induced constriction. However, after removal of spare postsynaptic vascular αi-adrenoceptors by treatment with the irreversible α-adrenoceptor antagonist phenoxybenzamine (5 × 10–8M, 1 × 10–7M), the α1-adrenoceptor-mediated vasconstrictor responses of phenylephrine became highly sensitive to antagonism by 8-bromo cGMP and nitroglycerin. These data suggest that the action of 8-bromo cGMP like nitroglycerin is ‘buffered’ by the presence of a large αi-adrenoceptor reserve in canine saphenous vein. The similarity in the efficacy and potency of these two agents suggests that the effects of nitroglycerin in canine saphenous vein may be the result of an increase in

ISSN:0031-7012    

DOI:10.1159/000138291

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Diltiazem (750 μg/kg plus 600 μg/kg/h × 1 h, i.v.) and vehicle were examined in open-chest anesthetized dogs subjected to 15 min of occlusion of the left circumflex coronary artery (LCCA). Regional segment lengths in myocardium supplied by the LCCA and by the left anterior descending coronary (LAD) were measured with piezoelectric crystals implanted in the subendocardium. Diltiazem decreased heart rate and mean arterial pressure, and increased coronary blood flow, determined with an electromagnetic flowmeter. Vehicle had no significant effects. Occlusion of the LCCA increased end diastolic segment length (EDL), and produced akinesis or paradoxical systolic lengthening: diltiazem -2.5 ± 2.7% and vehicle 0.0 ± 1.2% segmental shortening (SS). EDL and SS in the LAD zone showed small increases. After 15 min, the LCCA was reperfused and recovery of SS was followed for 3 h. Significantly greater recovery of SS was observed with diltiazem compared to vehicle throughout reperfusion: at 5 min, diltiazem 105 ± 22% and vehicle 43 ± 7% and at 180 min, diltiazem 73 ± 0% and vehicle 33 ± 8% of baseline SS. The LCCA and LAD zones both responded to isoproterenol 0.3 μg/kg given 2.5 h after reperfusion. During the isoproterenol challenge SS for LCCA in the diltiazem group (122 ± 21 %) was not different than that of vehicle (99 ± 15% of baseline). Calcium entry blockade with diltiazem resulted in improved myocardial function during reperfusion. The stunned myocardium showed significant stimulation of shortening by isoproterenol in

ISSN:0031-7012    

DOI:10.1159/000138292

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

CGS 10078B (CGS; l-[2,3-dihydro-l,4-(2S)-benzodioxm-2-yl]-5-[2,3-dihydro-1,4-(2i?)-benzodioxin-2-yl]-3-(1R,55)-aza-1,5-pentanediol methane sulfonate) is an agent with α- and β-receptor and calcium channel blocking actions. To study its antiarrhythmic activity, cats were anesthetized with α-chloralose, ventilated, and given atropine and gallamine. CGS (10 or 20 mg/kg, i.v.) was infused 15 min prior to ouabain. Bolus injections of ouabain (25 μg/kg, i.v.) were given every 15 min until death (D). Some cats were pretreated with reserpine (R; 5 mg/kg, i.p.) 24 h prior to the experiment. In other cats 6-hydroxydopamine (6-OHDA; 20 mg/kg, i.v.) was administered 3 days prior to CGS 20 mg/kg and ouabain. Data were compared with those of Lathers [Eur. J. Pharmacol. 64: 95, 1980], i.e., with 12 cats who received only ouabain and with 11 pretreated with timolol (T; 5 mg/kg, i.v.) prior to ouabain. After CGS (10 or 20 mg/kg, i.v.), but just prior to the first dose of ouabain, the blood pressure (BP) was decreased (p < 0.05) from control (165 ± 6 vs. 96 ± 7, and 136 ± 5 vs. 90 ± 10 mm Hg, respectively). Comparable heart rate (HR) values were also decreased (p < 0.05) from 225 ± 17 to 166 ± 14 and from 193 ± 8 to 152 ± 6beats/min. 11 min after T, BP and HR had decreased (p < 0.05) from 133 ± 6 to 103 ± 7 mm Hg and from 134 ± 4 to 104 ± 6 beats/min, respectively. Ouabain did not influence these decreases in BP and HR. CGS (10 or 20 mg/kg, i.v.) increased (p < 0.05) the time to ouabain-induced arrhythmia (AR) and D. The magnitude of the protection appeared to be similar to that afforded by T. R given prior to CGS (20 mg/kg, i.v.) also increased the time to ouabain-induced AR and D while 6-OHDA increased the time to AR. The CGS protection against ouabain-induced AR was still present in animals pretreated with R or 6-OHDA. This indicates that the antiarrhythmic affect is not dependent upon adrenergic ne

ISSN:0031-7012    

DOI:10.1159/000138293

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Pain and mental status were assessed in a series of 35 consecutive hospitalized patients with metastatic cancer receiving narcotics for pain that was difficult to control. Forty-five episodes of mental status impairment were detected in 27 of these patients. Fifteen patients had dose-related oversedation or organic brain syndrome. In only 4 could the narcotic dose be decreased without exacerbating the pain. Eleven patients had mental status impairment associated with factors other than the narcotic dose. These factors were: concurrent CNS-depressant drugs, presence of fever or infection, or changing from parenteral to average oral equianalgesic dose of narcotic. When these factors were corrected, mental function improved and remained stable despite resumption of the previous narcotic dose. Delirium occurred more frequently in patients over 65, while oversedation without delirium was more frequent in the younger group. For some patients with advanced metastatic cancer, pain relief and intact mental status cannot coexist. For others, correction of factors other than narcotics which can impair function can often lead to improved mental status without decreasing narcotic dose or decreasing the degree of pain control.

ISSN:0031-7012    

DOI:10.1159/000138294

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

The influence of phenobarbital on the activity of hepatic mixed function oxidases responsible for benzo[a]pyrene hydroxylation was studied in rats fed diets containing menhaden fish oil (rich in n-3 fatty acids). Male rats were starved for 2 days and refed diet devoid of fat or containing 0.5, 10, or 20% menhaden oil for 4 days. Phenobarbital increased the apparent Km value as well as Vmax for benzo[a]pyrene hydroxylase in microsomes from rats fed the 20% menhaden oil diet. The increased Km was due to a progressive decrease in benzo[a]pyrene metabolism at the lower substrate concentrations, even in the presence of increased cytochrome P-450 content. The phenobarbital-induced increase in Km and the decreases in benzo[a]pyrene hydroxylation were not observed in rats fed 0.5% menhaden oil or a diet devoid of fat.

ISSN:0031-7012    

DOI:10.1159/000138295

出版商:S. Karger AG    

年代:1987

数据来源: Karger

摘要:

Fifteen days of tolbutamide treatment significantly decreased the elimination half life (t½), area under the curve (AUC0→∞) and increased the clearance of sulphamethoxazole (SMZ) in rabbits. No significant difference was observed in the volume of distribution. The percentage of plasma protein binding to SMZ was not altered, while N-acetyltransferase activity in liver and kidney was significantly increased after tolbutamide therapy. The changes observed in the pharmacokinetic parameters of SMZ after tolbutamide treatment is due to the induction of liver N-acetyltransferase acti

ISSN:0031-7012    

DOI:10.1159/000138296

出版商:S. Karger AG    

年代:1987

数据来源: Karger