Biomedical subjects

M Johansson

Publications and source records attributed to M Johansson.

At least 145 records · Page 8Linked to original sources

PubMed1998

Distribution of estramustine in the BT4C rat glioma model.

Estramustine (EaM), a carbamate ester of 17beta-estradiol and nor-nitrogen mustard, is a cytotoxic compound with antitumoral effect in malignant glioma in vitro and in vivo . However, knowledge of the pharmacokinetics of EaM in experimental glioma is limited. The objective of this study was therefore to investigate further the distribution of EaM in the BT4C rat glioma model. Assessment of EaM uptake and distribution was performed by quantitative whole-body autoradiography. In addition, the uptake of EaM and its metabolites estromustine (EoM), estradiol, and estrone were analyzed by gas chromatography. EaM was taken up from the circulation and was found to be the main product in glioma tissue. Whole-body autoradiography after [14C]-EaM administration revealed a strong 14C label simultaneously in tumor and normal brain tissue at 0.5 h after drug administration. In tumor tissue, sustained high levels of 14C label were detected at 12 h after drug administration. In contrast to the tumor, radioactivity in normal brain tissue rapidly leveled off, indicating a retention of radioactivity in the tumor. The tumor/brain radioactivity ratio reached a peak of 4.5 at 12 h after drug administration. High levels of 14C label were also found in pulmonary tissue. By gas chromatography, EoM was found to be the main metabolite in plasma. However, EaM reached higher levels in tumor tissue, with the mean tumor/plasma ratio being 11.7 as compared with 2.0 for EoM. Only low plasma levels of the estrogen metabolites were detected. In conclusion, EaM is taken up in the BT4C rat glioma tissue and is retained in the tumor as compared with normal brain tissue and plasma. EaM showed a greater selectivity for tumor tissue, exhibiting a high tumor/plasma ratio as compared with EoM. The distribution pattern after administration of EaM, as evaluated by both whole-body autoradiography and gas chromatography, supports the earlier suggestion that the uptake is related to a protein with EaM-binding characteristics.

Animals↗

PubMed1998

The relation of weight, length and ponderal index at birth to body mass index and overweight among 18-year-old males in Sweden.

The intrauterine environment seems to be important for the occurrence of cardiovascular and other chronic diseases in adulthood. The aim of the present study is to analyze the importance of birthweight, birthlength and Ponderal Index (PI) for Body Mass Index (BMI) and overweight at 18 years of age. In this cohort study, the nationwide Swedish Medical Birth Registry for the years 1973-1976 was linked with the national Military Service Conscription Registry for 1990-1996. Of 193,056 children born at term 1973-1976, 165,109 (85.5%) could be followed-up at 18 years of age. The children were divided into percentile groups according to birthweight and birthlength for each gestational week. They were also assigned to three different categories, according to birthweight and birthlength for each gestational week: infants with values < or = 5th percentile, values > 5th and < or = 95th percentile, and values > 95th percentile. Clear-cut associations were found between birthweight and BMI, and between PI at birth and BMI at 18 years of age. High birthweight and normal birthlength and also high birthweight and high birthlength for gestational age were found to be risk factors for overweight and severe overweight among young men in Sweden.

Adolescent↗

PubMed1998

Dichotic speech tests.

When central auditory dysfunction is present, ability to understand speech in difficult listening situations can be affected. To study this phenomenon, dichotic speech tests were performed with test material in the Swedish language. Digits, spondees, sentences and consonant-vowel syllables were used as stimuli and the reporting was free or directed. The test material was recorded on CD. The study includes a normal group of 30 people in three different age categories; 11 years, 23-27 years and 67-70 years. It also includes two different groups of subjects with suspected central auditory lesions; 11 children with reading and writing difficulties and 4 adults earlier exposed to organic solvents. The results from the normal group do not show any differences in performance due to age. The children with reading and writing difficulties show a significant deviation for one test with digits and one test with syllables. Three of the four adults exposed to solvents show a significant deviation from the normal group.

Adult↗

PubMed1998

Long-term tacrine treatment in three mild Alzheimer patients: effects on nicotinic receptors, cerebral blood flow, glucose metabolism, EEG, and cognitive abilities.

The effect of long-term treatment with tacrine (tetrahydroaminoacridine) was studied in three Alzheimer patients (aged 57, 64, and 68 years) with mild dementia. All three patients had a Mini-Mental State Examination score of 24/30 and carried at least one apolipoprotein E (ApoE) epsilon4 allele. Tacrine was given in doses between 80 and to 160 mg daily for 13-31 months. A lower tacrine concentration was observed generally in cerebrospinal fluid (CSF) compared with plasma. The acetylcholinesterase activity in CSF tended to be increased following longer periods of tacrine treatment, whereas the butyrylcholinesterase activity was decreased. The three patients repeatedly underwent positron emission tomography investigation of cerebral blood flow, nicotinic receptors, cerebral glucose metabolism, and electroencephalogram (EEG) and cognitive tests. Positive influences on these parameters were observed following both short-term and long-term treatment with tacrine. Improvement of nicotinic receptors (measured as 11C-nicotine binding), cerebral blood flow, EEG, and some cognitive tests (trail making test, block design test) occurred earlier after initiation of tacrine treatment compared with the glucose metabolism, which was increased after several months of tacrine treatment. An improvement in attention (trail making test) was observed following tacrine as sign for frontal lobe activation (EEG). The functional effects of tacrine in Alzheimer patients appeared to be related to both dose and length of cholinesterase inhibitor treatment.

Aged↗

PubMed1998

Gangliosides in cerebrospinal fluid in children with autism spectrum disorders.

Gangliosides are sialic acid-containing glycolipids found in all cells, especially abundant in nerve cells and mainly situated on outer-membrane surfaces. The aim of this study was to provide data on the concentration of gangliosides in the CSF of children and adolescents with autism spectrum disorders (ASD) - 66 with autistic disorder, and 19 with other autism spectrum disorders. The comparison group consisted of 29 children and adolescents, whose CSF had been sampled to exclude acute infectious CNS disorder. The concentrations of the gangliosides GM1, GD1a, GD1b, and GT1b were determined using a microimmunoaffinity technique. The ASD group had a significantly higher concentration of ganglioside GM1 compared with the comparison group. The GM1 increase could not be explained as secondary to other clinical factors. Mean ganglioside levels did not differentiate subgroups with autistic disorder and those with a more atypical clinical picture, nor subgroups with known medical disorders and those with idiopathic autism. Altered patterns of gangliosides in the CNS might reflect important correlates of pathogenesis in autism.

Adolescent↗

PubMed1998

Structure-activity relationship for inhibition of CYP11B1-dependent glucocorticoid synthesis in Y1 cells by aryl methyl sulfones.

The effects of xenobiotics on CYP11B1-dependent corticosterone synthesis (11 beta-hydroxylase) in mouse adrenocortical Y1 cells were studied. 3-Methylsulfonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene (MeSO2-DDE) and some methylsulfonyl polychlorinated biphenyls (MeSO2-PCB) inhibited the corticosterone synthesis, whereas PCBs or DDE did not. This indicates a crucial role of the methyl sulfone group for this inhibitory effect. Kinetic analyses of MeSO2-DDE and the two most potent MeSO2-PCBs were conducted using Lineweaver-Burk double-reciprocal plots. The data showed a competitive inhibition of CYP11B1 by the compounds, with apparent inhibitory constants (Ki) of 1.6, 4.6, and 6.7 microM for MeSO2-DDE, 4-MeSO2-2,3,6,4'-tetrachlorobiphenyl, and 4-MeSO2-2,3,6,3',4'-pentachlorobiphenyl, respectively. For comparison, the substrate K(m) was 3.5 microM in the cells, and metyrapone and ketoconazole had apparent Ki-values of 0.8 and 0.04 microM, respectively. In contrast to all previously known inhibitors of CYP11B1, the aryl methyl sulfones are the first examples of CYP11B1 inhibitors not being heterocyclic amines or steroids. The aryl methyl sulfones are widespread environmental pollutants and their inhibition of CYP11B1 constitutes another potential mechanism for endocrine disruption. Their influence on the synthesis of adrenocortical hormones thus merits further interest.

Adrenal Cortex↗

PubMed1998

Differential intracellular compartmentalization of herpetic thymidine kinases (TKs) in TK gene-transfected tumor cells: molecular characterization of the nuclear localization signal of herpes simplex virus type 1 TK.

The thymidine kinases (TKs) of herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) were expressed in human osteosarcoma cells as fusion proteins with the green fluorescent protein (GFP), and their intracellular localizations were determined. The three TK-GFP fusion products were localized in different subcellular compartments of the transfected tumor cells. HSV-1 TK-GFP was localized exclusively in the nucleus, HSV-2 TK-GFP was predominantly found in the cytosol, while VZV TK-GFP was localized in both the nucleus and the cytosol. In support of these findings, we identified a nuclear localization signal (NLS) in the N-terminal arginine-rich region of HSV-1 TK that was absent in HSV-2 and VZV TK. The first 34 amino acids proved necessary for the specific nuclear localization of HSV-1 TK and, when added to the VZV TK-GFP gene construct, also sufficed to specifically target VZV TK-GFP to the nucleus. Further analysis of this NLS through site-directed mutagenesis revealed that the basic amino acid-rich nonapeptide 25R-R-T-A-L-R-P-R-R33 is of crucial importance in the nuclear targeting of HSV-1 TK. In particular, we revealed that the presence of the arginine residues at positions 25, 26, 30, 32, and 33 is obligatory for efficient NLS functioning, whereas arginine and histidine residues outside of the nonapeptide (i.e., residues R18, R20, and H22) did not change the functional properties of the NLS.

Amino Acid Sequence↗

PubMed1998

Effects on heart rate variability of isosorbide-5-mononitrate and metoprolol in patients with recent onset of angina pectoris.

BACKGROUND: Beta-blockers reduce sympathetic tone, increase vagal tone and improve prognosis in ischaemic heart disease. Nitroglycerin, being a vasodilator, may theoretically have an opposite effect and worsen the prognosis. The purpose of the present study was to analyse heart rate variability (HRV), which reflects autonomic tone, in angina patients on isosorbide-5-mononitrate (IS-5-MN) and/or metoprolol. METHODS AND RESULTS: Thirty-two patients (32-81 years old), with recently developed angina (median duration: 3 months), showing no other disease and on no drugs, were Holter-monitored 24-48 h at baseline and after 4-5 days on IS-5-MN (mean daily dose: 33 mg), on metoprolol (mean daily dose: 184 mg) and on the combined treatment. Recordings were analysed on the Marquette Series 8000 Holter scanner. Both IS-5-MN and metoprolol significantly reduced myocardial ischaemia (ST integral) and ventricular tachycardias. Metoprolol induced significant changes in the following parameters (baseline versus metoprolol): high-frequency peak 9 +/- 4 versus 11 +/- 4 ms (p < 0.001), low-to-high frequency ratio 2.5 +/- 0.6 versus 1.9 +/- 0.6 (p < 0.0001), root mean square of RR interval difference 23 +/- 7 versus 31 +/- 9 ms (p < 0.0001), RR intervals differing more than 50 ms from the preceding one 4.8 +/- 3.9 versus 10.0 +/- 7.0% (p < 0.0001), mean of all 5-min standard deviations 50 +/- 12 versus 56 +/- 11 ms (p < 0.001) and mean RR interval 819 +/- 90 versus 1,019 +/- 120 ms (p < 0.00001). The combined treatment caused approximately the same HRV changes as metoprolol alone. IS-5-MN had no significant effect on any HRV parameter, neither alone nor in combination with metoprolol. CONCLUSION: A clinically effective dose of metoprolol had potentially positive effects on HRV with increase in vagal and decrease in sympathetic tone while IS-5-MN had no effect on HRV, neither positive nor negative, neither alone nor in combination with metoprolol.

Adrenergic beta-Antagonists↗

PubMed1998

Interactions between methylsulfonyl PCBs and the glucocorticoid receptor.

Persistent polychlorinated biphenyl (PCB) metabolites were studied with respect to their interaction with the human glucocorticoid receptor (GR). 3-Methylsulphonyl-2,5,6,2',4',5'-hexachlorobiphenyl (3-MeSO2-CB149) was shown to compete with 3H-dexamethasone for binding to the GR, with an IC50 (concentration that inhibits 50%) of approximately 1 microM. Using GRAF cells expressing human GR, glucocorticoid responsive element, and a reporter enzyme, we demonstrated that 3-MeSO2-CB149 functionally acts as an antagonist at the GR (IC50 = 2.7 microM). In accordance with the receptor binding, the antagonism mainly appeared to be of a competitive nature. When studying the competitive binding of 24 methylsulfonyl PCBs (relative to dexamethasone) to GR from mouse liver cytosol, seven compounds had a higher affinity to GR than 3-MeSO2-CB149. Structure-activity relationship studies indicated that the presence of three chlorine atoms in the ortho-position and chlorine and methyl sulfone groups on either end of the molecule (4 and 4'-position) increased the affinity to GR. The relevance of this finding for human health is not known, but PCB methyl sulfones are ubiquitous pollutants present in mother's milk. The results stress the need for studying endocrine disruptors that affect hormonal systems other than sex and thyroidogenic hormones.

Animals↗

PubMed1998

The puzzle of autism: an ophthalmologic contribution.

PURPOSE: A previous study of 86 thalidomide-affected subjects with ophthalmic manifestations revealed the unexpected finding of autism in 4 of the 5 severely retarded individuals. The subjects had anomalies associated with an early gestational effect of thalidomide, including facial nerve palsy and incomitant strabismus. Because autism has been observed in a few cases of Möbius sequence (Möbius syndrome), a condition characterized by involvement of the sixth and seventh cranial nerves, the similarity to early thalidomide embryopathy suggested a relation between cranial nerve involvement and autism. The present study was undertaken to further evaluate the association of autism with patients manifesting findings of Möbius syndrome. METHODS: A prospective study of 25 Swedish patients with Möbius sequence was conducted. The patients had a complete multidisciplinary evaluation, including ophthalmologic and psychiatric examinations and standard testing for autism. Findings associated with autism were compared with the ocular and systemic anomalies of the 4 thalidomide-affected subjects. RESULTS: In the Möbius group 6 patients had autism, achieving the criteria for autism according to all the diagnostic manuals that were used. One patient showed autistic-like conditions meeting fewer numbers of the criteria. A few were too young to be meeting evaluated. Incomitant strabismus ranging from primary abduction defects alone to a horizontal gaze paresis pattern was noted in these patients, in addition to characteristic findings of seventh nerve paresis. Aberrant lacrimation was observed in many cases, especially often associated with autism. CONCLUSION: The common group of anomalies noted in both cases of thalidomide embryopathy and Möbius sequence suggests that brain-stem damage probably early in embryogenesis can sometimes be associated with autism.

Abnormalities, Drug-Induced↗

PubMed1998

Kinetics, localization and characteristics of B- and T-cell responses to iscoms containing human influenza virus glycoproteins.

B- and T-cell responses have been studied after primary and secondary immunizations of mice with iscoms containing influenza virus envelope glycoproteins. After primary immunization both B- and T-cell responses were initiated in the draining lymph nodes. T-cells showed peak activity with respect to proliferation and cytokine production after five to eight days and the highest number of IgG secreting cells (IgG-SC) was recorded at day seven. The responses in the spleen developed slowly but were of longer duration. Cytokines produced by spleen cells included high levels of IFN-gamma and IL-2. After a secondary immunization the frequencies of IgG-SC were drastically increased in both LN and spleen, but decreased rapidly with time. At day eight after the secondary immunization high numbers of IgG-SC were detected in the bone marrow. High titres of IgG1 and IgG2a and substantial titres of IgG2b and IgG3 were detected in serum.

Adjuvants, Immunologic↗

PubMed1997

Human deoxycytidine kinase is located in the cell nucleus.

Human deoxyribonucleoside kinases are required for the pharmacological activity of several clinically important anticancer and antiviral nucleoside analogs. Human deoxycytidine kinase and thymidine kinase 1 are described as cytosolic enzymes in the literature, whereas human deoxyguanosine kinase and thymidine kinase 2 are believed to be located in the mitochondria. We expressed the four human deoxyribonucleoside kinases as fusion proteins with the green fluorescent protein to study their intracellular locations in vivo. Our data showed that the human deoxycytidine kinase is located in the cell nucleus and the human deoxyguanosine kinase is located in the mitochondria. The fusion proteins between green fluorescent protein and thymidine kinases 1 and 2 were both predominantly located in the cytosol. Site-directed mutagenesis of a putative nuclear targeting signal, identified in the primary structure of deoxycytidine kinase, completely abolished nuclear import of the protein. Reconstitution of a deoxycytidine kinase-deficient cell line with the wild-type nuclear or the mutant cytosolic enzymes both restored sensitivity toward anticancer nucleoside analogs. This paper reports that a deoxyribonucleoside kinase is located in the cell nucleus and we discuss the implications for deoxyribonucleotide synthesis and phosphorylation of nucleoside analogs.

Amino Acid Sequence↗

PubMed1997

Cloning of the cDNA and chromosome localization of the gene for human thymidine kinase 2.

Human thymidine kinase 2 (TK2) is a deoxyribonucleoside kinase that phosphorylates thymidine, deoxycytidine, and deoxyuridine. The enzyme also phosphorylates anti-viral and anti-cancer nucleoside analogs. We have identified an expressed sequence tag cDNA that encoded a 27.5-kDa protein approximately 30% similar to the human deoxycytidine kinase and deoxyguanosine kinase. The protein was expressed in Escherichia coli and shown to have similar substrate specificity as reported for purified native human TK2. The recombinant TK2 was shown to phosphorylate the anti-cancer nucleoside analog 2',2'-difluorodeoxycytidine. Northern blot analysis showed two mRNA species at 2.4 and 4.0 kilobases predominantly expressed in liver, pancreas, muscle, and brain. We identified a sequence-tagged site designed from the 3' region of the TK2 cDNA. The sequence-tagged site has been mapped to 81-84 centimorgans from the top linkage group of chromosome 16, which corresponds to the 16q22 region. Our data show that deoxycytidine kinase, deoxyguanosine kinase, and TK2 belong to a family of closely related enzymes. At the time of this report all four of the known human deoxyribonucleoside kinases have been cloned. This provides the opportunity to characterize their individual contribution to therapeutic and toxic effects of nucleoside analogs.

Amino Acid Sequence↗

PubMed1997

Chiral assay of atenolol present in microdialysis and plasma samples of rats using chiral CBH as stationary phase.

Two different enantioselective chiral chromatographic methods were developed and validated to investigate the disposition of the beta 1-receptor antagonist atenolol in blood and in brain extracellular fluid of rats (tissue dialysates). System A for the plasma samples was a one-column chromatographic system with a chiral CBH column with an aqueous buffer as mobile phase into which cellobiose was added for selective regulation of the retention of the internal standard, (S)-metoprolol. The plasma samples were analysed after a simple extraction procedure. The limit of quantitation was 0.2 micrograms/ml for the atenolol enantiomers. The repeatability of the medium concentration quality control plasma sample (6.0 micrograms rac-atenolol/ml) was 11-18% for the enantiomers. The dynamic linear range of the plasma samples was 0.5-20 micrograms/ml. For system B, since atenolol is an extremely hydrophilic drug, the tissue dialysate sample required a much more sensitive system as compared to the plasma samples. A coupled column system was used for peak compression of the enantiomers in the eluate after the separation on the Chiral CBH column, hence increasing the detection sensitivity. The limit of quantification was 0.045 micrograms/ml for the atenolol enantiomers in artificial CSF. The repeatability of the medium concentration quality control samples (0.1 and 4.0 micrograms rac-atenolol/ml in artificial CSF and Hepes Ringer, respectively) was 2.8-9.3% for the two enantiomers. The dynamic linear range of the brain samples was 0.05-1.0 and 0.5-20 micrograms/ml in artificial CSF and Hepes Ringer, respectively.

Adrenergic beta-Antagonists↗

PubMed1997

Lack of F1 anti-parental resistance in H-2b/d F1 hybrids devoid of beta2-microglobulin.

F1 hybrid mice often reject parental hematopoietic grafts, a phenomenon known as hybrid resistance. Hybrid resistance is mediated by natural killer (NK) cells and although the molecular interactions responsible for this phenomenon are largely unknown, one hypothesis suggests that parental cells are rejected because they fail to express a complete set of host major histocompatibility complex (MHC) class I molecules. Inherent in this theory is that NK cells in the F1 hybrid are instructed by self MHC class I molecules to form an NK cell repertoire capable of reacting against cells lacking these self MHC class I molecules. Here, we show that C57BL/6 x DBA/2 mice (H-2b/d) devoid of beta2-microglobulin (beta2m) are incapable of rejecting beta2m-/- parental C57BL/6 cells (H-2b) both in vivo and in vitro. From this, we conclude that the development of an NK cell repertoire, at least in F1 mice of the H-2b/d haplotype, requires expression of MHC class I molecules complexed with beta2m.

Animals↗

PubMed1997

Decrement of blood flow precedes the involution of the ventral prostate in the rat after castration.

Blood flow to the rat ventral prostate (VP), dorsolateral prostate (DP), and Dunning R3327 prostatic tumors was measured at different times up to 7 days after castration, using the microsphere method. In the VP organ weight was decreased from day 3 onwards. Blood flow was, however, already significantly decreased from day 1. The reduced blood flow in VP in 1-3 and 7-day castrated animals could be reversed by testosterone treatment. Organ weight was slightly decreased but blood flow was unaffected by castration in DP. Castration left Dunning tumor volume and blood flow unaffected. Using immunohistochemistry, androgen receptors were observed in epithelial and stromal cells in VP, DP and Dunning tumors, but not in blood vessels. Castration is known to induce apoptosis in the VP, but not in the DP or in Dunning tumors. This suggests that a reduction in blood flow might be an important component for the castration-induced involution and apoptosis in prostatic tissue. The reason why castration reduces blood flow only in the VP, and not in the DP or Dunning tumor is unknown.

Animals↗

PubMed1997

A dose-response study comparing suppression of plasma cortisol induced by fluticasone propionate from Diskhaler and budesonide from Turbuhaler.

OBJECTIVE: To compare the systemic potency of inhaled fluticasone propionate delivered via Diskhaler (FP-DH), and inhaled budesonide delivered via Turbuhaler (BUD-TBH) over the clinically recommended dose range using plasma cortisol suppression as a marker for systemic activity. METHODS: The systemic potency was examined in a dose-response study in 81 healthy male volunteers. The study was of an open, randomized, parallel-group (four groups) design, where two treatments were given in crossover fashion within each group. FP-DH and BUD-TBH were given b.i.d. for 7 days (14 doses): 100 and 100 micrograms (group 1); 200 and 200 micrograms (group 2); 500 and 400 micrograms (group 3); 1000 and 800 micrograms (group 4). There was a washout period of 7 days within each treatment group. All doses were administered at 08:00 and 20:00 hours. Multiple plasma cortisol samples were taken every 2 h over 24-h periods prior to randomization (baseline) and during steady state (i.e., the last two dosing intervals). Cortisol suppression was determined by comparing average plasma concentrations of cortisol before and during treatment. Dose-response curves for cortisol suppression were analyzed using multivariate non-linear regression (Hill modeling). RESULTS: Multiple dosing for 7 days with FP-DH and BUD-TBH resulted in dose-dependent cortisol suppression by both drugs, most pronounced at the two highest dose levels. FP-DH-induced suppression was 41% at 500 micrograms and 86% at 1000 micrograms b.i.d., while that induced by BUD-TBH was 19% at 400 micrograms and 47% at 800 micrograms b.i.d. Statistically significant differences were found when comparing the two steroids at these two dose levels. Doses producing 50% of maximum suppression (ED50) were estimated at 833 micrograms b.i.d. for BUD-TBH and 479 micrograms b.i.d. for FP-DH. This gave an estimated relative cortisol suppression over the dose range of 1.74:1 (FP-DH:BUD-TBH). ED50 values, estimated from cortisol concentrations at 08:00 hours (12 h after the last dose), were 1212 micrograms b.i.d. for BUD-TBH and 527 micrograms b.i.d. for FP-DH giving a relative cortisol suppression of 2.30:1 (FP-DH:BUD-TBH). Fourteen subjects on the highest FP-DH dose and 3 at the next highest dose had morning plasma cortisol levels below the lower reference limit. No subject taking budesonide, however, had morning plasma cortisol levels below the reference limit. Analysis of the time for return to pretreatment baseline levels showed that cortisol suppression, 12-24 h after the last dose, was statistically significant compared with the baseline for the highest dose of FP-DH but not for any of the BUD-TBH doses. CONCLUSIONS: The results of the present study show that FP-DH suppresses plasma cortisol more than BUD-TBH on a equivalent basis with regard to both magnitude and duration.

Administration, Inhalation↗

PubMed1997

The effects of enalapril on the natriuretic response evoked by an oral sodium load in sodium deprived normotensive and hypertensive rats.

Previous studies have shown that an oral sodium load during sodium deprivation is excreted faster than an intravenous load. We wanted to study whether the renin-angiotensin-aldosterone system might be associated with this phenomenon and therefore the influence of the angiotensin converting enzyme (ACE) inhibitor enalapril was investigated. The experiments were performed on four strains of rat: spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, inbred hypertension-prone (SS/Jr) and hypertension-resistant (SR/Jr) Dahl rats. In SHR and WKY rats pretreated with enalapril it was observed that an intravenous sodium load induced a renal sodium excretion which was between two and five times larger than that seen after an oral load. In SR/Jr and SS/Jr rats the sodium excretion was the same regardless of the route of administration. In SS/Jr rats sodium excretion increased three- to fourfold upon sodium repletion, whereas no significant increase was observed in SR/Jr rats. Thus, the present results indicate that an intact renin-angiotensin system is necessary for the interplay between the gastrointestinal tract and kidney.

Administration, Oral↗