摘要:

The effect of xamoterol on ischemic myocardial pH was examined in dogs. Partial occlusion of the left anterior descending coronary artery (LAD) decreased myocardial pH from 7.52–7.63 to 6.80–6.85. Xamoterol was injected intravenously 30 min after LAD occlusion that lasted for 90 min. Xamoterol (30 or 70 μg/kg) increased the myocardial pH that had been decreased by partial occlusion, the degree of pH increase being greater with 30 μg/kg than with 70 μg/kg, but at the dose of 200 μg/kg it did not increase. In the nonischemic normal heart, xamoterol (30 or 70 μg/kg, i.v.) had no marked effect on hemodynamic parameters, but the drug (200 μg/kg, i.v.) increased contractile force and heart rate with a transient decrease of myocardial pH. It is concluded that only the small dose (30 or 70 μg/kg) of xamoterol is effective in restoring the myocardial pH that has been decreased by partial occlusion

ISSN:0031-7012    

DOI:10.1159/000138231

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Isolated rat hepatocytes were used to determine the relationship between magnitude of uptake by cells and cytotoxic effects of chlorpromazine (CPZ) and promazine (PZ). Cell injury was evaluated by the extent of leakage of cytoplasmic and lysosomal enzymes from cells to surrounding medium and by cytopathic changes seen under surface scanning electron microscopy, after drug exposure. The drug uptake was time- and dose-dependent; cell preparations exposed to equal concentrations of either drug in the medium contained a twice greater concentration of CPZ than of PZ. Cytoplasmic and lysosomal enzyme leakage from cells exposed to 200 and 500 μM of CPZ showed significantly greater toxicity than control cells or those exposed to PZ at the same concentration. Surface activity of drugs was determined to calculate their surface excess. The surface pressure of CPZ is about twice that of PZ at equimolar concentration and correlated with extent of drug uptake and toxicity, suggesting that the surfactibility could play a role in bioavailability and toxicity of these drugs to liver cell membranes. Cytotoxicity was decreased by entrapment of CPZ inside liposomes; up to 40% for lactate dehydrogenase leakage and 47% of β-glucuronidase, presenting further evidence for the potential use of liposome

ISSN:0031-7012    

DOI:10.1159/000138232

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

Monoamine and metabolite levels were determined in brain regions and in the kidney, heart and adrenals taken from Dahl salt-sensitive (DS) and salt-resistant (DR) rats on either normal (NS) or high (HS) (8.5% NaCl) salt diets. The HS diet significantly (p < 0.01) elevated blood pressure only in DS rats. DS-HS rats had a significantly (p < 0.001) greater increase in renal weight and a significantly (p < 0.001) greater reductions in renal norepinephrine (NE) content and concentration than the DR-HS rats. Cardiac NE content and concentration were also lower (p < 0.001) in DS rats when compared to DR rats. Adrenal catecholamines were also altered in DS rats. There were genetic differences in brain regional levels of NE, dopamine (DA) and serotonin (5-HT) between DR and DS rats. NE levels were significantly (p < 0.03) higher in DS compared to DR rats in the pons and hypothalamus. DA levels were significantly (p < 0.01) greater in the striatum of DS compared to DR rats as were 5-HT levels in the striatum and cortex. HS diets had no effect on brain monoamine or metabolite levels in either DS or DR rats except to elevate cortical 5-hydroxyindoleacetic acid levels. The cardiovascular implications of these genetic and salt-related changes in peripheral and central nervous system monoamines were discussed.

ISSN:0031-7012    

DOI:10.1159/000138233

出版商:S. Karger AG    

年代:1986

数据来源: Karger

摘要:

The antihypertensive effect of chronic administration of L-tyrosine (Tyr) was investigated in a two-part study. In the first experiment, adult male Sprague-Dawley rats were assigned to 1 of 4 treatment groups: (1) control diet plus unilateral nephrectomy (Nphx) and 0.15 M NaCl (Sal) as the sole drinking solution (C-CTRL); (2) control diet plus deoxycorticosterone acetate (DOCA, 268 μg/rat/day), Nphx, and Sal (C-DOCA); (3) control diet supplemented with 2.5% L-p-Tyr plus Nphx and Sal (Tyr-CTRL), and (4) Tyr plus DOCA, Nphx, and Sal (Tyr-DOCA). Systolic blood pressure (SBP) increased within 2 weeks after initiation of treatment with DOCA-salt and remained elevated throughout the duration (8 weeks) of the study (p < 0.001). Dietary administration of Tyr to DOCA-treated rats failed either to affect SBP in normotensive rats or the elevation of SBP in DOCA-treated rats. Dietary supplementation with Tyr induced a significant elevation in urinary excretion of free dopamine (week 1, 3, 5, and 7) and a decreased excretion of free norepinephrine (week 1) without regard to DOCA treatment. Metabolic reponsiveness (change in colonic temperature) and cardiovascular responsiveness (change in heart rate) to subcutaneous administration of the β-adrenergic agonist, isoproterenol, were significantly prolonged while α2-adrenoceptor number (cerebral cortical membranes; 3H-yohimbine binding) was reduced in rats receiving Tyr. In the second experiment, similar rats were assigned to 1 of 3 treatment groups: (1) control diet plus Nphx and Sal, (2) control diet plus Nphx, DOCA and Sal, and (3) Tyr plus DOCA, Nphx, and Sal; however, Tyr was not started until DOCA-salt-induced hypertension developed (4 weeks). Neither acute (2.5 h post-meal) nor chronic (4 weeks) effects of administration of Tyr on SBP were noted. Thus, the Tyr-induced changes observed in these studies include a chronic increase in free dopamine, and a transient decrease in norepinephrine, excretion. No significant effects of Tyr on blood pressure of DOCA-salt-treated rats were observ

ISSN:0031-7012    

DOI:10.1159/000138234

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138235

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138236

出版商:S. Karger AG    

年代:1986

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138230

出版商:S. Karger AG    

年代:1986

数据来源: Karger