Biomedical subjects

C Bock

Publications and source records attributed to C Bock.

At least 19 recordsLinked to original sources

PubMed2006

Effects of environmental hypercapnia on animal physiology: a 13C NMR study of protein synthesis rates in the marine invertebrate Sipunculus nudus.

Global climate change is associated with a progressive rise in ocean CO(2) concentrations (hypercapnia) and, consequently, a drop in seawater pH. However, a comprehensive picture of the physiological mechanisms affected by chronic CO(2) stress in marine biota is still lacking. Here we present an analysis of protein biosynthesis rates in isolated muscle of the marine invertebrate Sipunculus nudus, a sediment dwelling worm living at various water depths. We followed the incorporation of (13)C-labelled phenylalanine into muscular protein via high-resolution NMR spectroscopy. Protein synthesis decreased by about 60% at a medium pH of 6.70 and a consequently lowered intracellular pH (pHi). The decrease in protein synthesis rates is much stronger than the concomitant suppression of protein degradation (60% versus 10-15%) possibly posing a threat to the cellular homeostasis of structural as well as functional proteins. Considering the progressive rise in ocean CO(2) concentrations, permanent disturbances of cellular protein turnover might seriously affect growth and reproductive performance in many marine organisms with as yet unexplored impacts on species density and composition in marine ecosystems.

Animals↗

PubMed2004

The strengths of in vivo magnetic resonance imaging (MRI) to study environmental adaptational physiology in fish.

Adaptational physiology studies how animals cope with their environment, even if this environment is subject to permanent fluctuations such as tidal or seasonal variations. Aquatic organisms are generally more prone to be exposed to osmotic, hypoxic and temperature challenges than terrestrial animals. Some of these challenges are more restraining in an aquatic environment. To date, very few studies have used in vivo magnetic resonance imaging (MRI) to uncover the physiological mechanisms that respond to or compensate for these challenges. This paper provides an overview of what has been accomplished thus far by using MRI to study the environmental physiology of fish. It introduces the reader to the use of small teleost fish such as carp (12 cm, 60 g) and eelpout (25 cm, 50 g) as models for such research and to provide new perceptions into the applicability of MRI tools based on new insights into the nature of MRI contrast. Representative MRI studies have made contributions to the identification of the lack of cell volume repair in stenohaline fish during osmotic stress. They have studied the underlying physiological mechanisms of brain anoxia tolerance in fish and have qualified the role of the cardio-circulatory system in setting thermal tolerance windows of fish.

Adaptation, Physiological↗

PubMed2004

Oxygen limited thermal tolerance in fish?--Answers obtained by nuclear magnetic resonance techniques.

In various phyla of marine invertebrates limited capacities of both ventilatory and circulatory performance were found to set the borders of the thermal tolerance window with limitations in aerobic scope and onset of hypoxia as a first line of sensitivity to both cold and warm temperature extremes. The hypothesis of oxygen limited thermal tolerance has recently been investigated in fish using a combination of non-invasive nuclear magnetic resonance (NMR) methodology with invasive techniques. In contrast to observations in marine invertebrates arterial oxygen tensions in fish were independent of temperature, while venous oxygen tensions displayed a thermal optimum. As the fish heart relies on venous oxygen supply, limited cardio-circulatory capacity is concluded to set the first level of thermal intolerance in fish. Nonetheless, maximized ventilatory capacity is seen to support circulation in maintaining the width of thermal tolerance windows. The interdependent setting of low and high tolerance limits is interpreted to result from trade-offs between optimized tissue functional capacity and baseline oxygen demand and energy turnover co-determined by the adjustment of mitochondrial densities and functional properties to a species-specific temperature range. At temperature extremes, systemic hypoxia will elicit metabolic depression, thereby widening the thermal window transiently sustained especially in those species preadapted to hypoxic environments.

Acclimatization↗

PubMed2003

CpG-A oligonucleotides induce a monocyte-derived dendritic cell-like phenotype that preferentially activates CD8 T cells.

Human B cells and plasmacytoid dendritic cells recognize CpG motifs within microbial DNA via Toll-like receptor 9. Two functionally distinct types of CpG motif containing oligonucleotides (CpG ODN) have been described, CpG-A and CpG-B. In contrast to CpG-B, CpG-A induces high amounts of type I IFN (IFN-alpha and IFN-beta) in plasmacytoid dendritic cells. In the present study, we examined the effects of CpG-A on human primary monocytes. In PBMC stimulated with CpG-A and GM-CSF, monocytes showed excellent survival, increased in size and granularity, and within 3 days developed a dendritic cell-like phenotype that was characterized by down-regulation of CD14, partial up-regulation of CCR7, and an increased surface expression of costimulatory and Ag-presenting molecules. This effect could be inhibited by a combination of blocking Abs to type I IFN, and no such CpG-A-induced changes were observed in purified monocytes. Although IL-12 production by this dendritic cell-like phenotype required additional stimulation with CD40 ligand, this cell type spontaneously up-regulated IL-15 expression. Consistent with the known effect of IL-15 on effector and memory CD8 T cells, the frequency of CCR7(-)/CD45RA(-) CD8 T cells was selectively increased in allogeneic T cell assays. Furthermore, this dendritic cell type was more potent to support both the generation and the IFN-gamma production of autologous influenza matrix peptide-specific memory CD8 T cells as compared with dendritic cells generated in the presence of GM-CSF and IL-4. In conclusion, monocytes exposed to the cytokine milieu provided by CpG-A rapidly develop a dendritic cell-like phenotype that is well equipped to support CD8 T cell responses.

Adjuvants, Immunologic↗

PubMed2003

The NCI/CIT microArray database (mAdb) system - bioinformatics for the management and analysis of Affymetrix and spotted gene expression microarrays.

A scalable, modular, enterprise-level system for both microarray databasing and analysis over the Internet has been developed over the past four years by the National Cancer Institute's Center for Cancer Research in collaboration with NIH's Center for Information Technology. This completely Web-based system, called mAdb (for microArray database), is currently supporting over 810 registered users and collaborators at NIH and contains over 22,000 microarray experiments, making it one of the largest collections of microarray data in existence. In addition, the mAdb system has been ported for the Netherlands Cancer Institute, the Genome Institute of Singapore, and the CDC. This system has been used for a wide variety of scientific experiments spanning the range from cancer to studies of early development, and for human, mouse, rat, yeast, and numerous microbial organisms.

Animals↗

PubMed2003

Review of laparoscopic and open colorectal surgery in the "Zitha" Hospital (Luxembourg) in the year 2002.

BACKGROUND: A review and outcome of laparoscopic colorectal surgery in the visceral surgery unit in the Zitha Hospital for the year 2002. METHODS: All patients, presenting with benign or malignant disease of the colon or rectum were evaluated. Depending on the tumour size, a laparoscopic approach is advocated whenever possible. Operation and patient specific factors (age, duration of the procedure and duration of hospital stay, diagnosis of malignant tumour versus benign disease, conversion and complication rate) are presented. Patients who had to be converted are classified under the open surgery group. RESULTS: A total of 103 laparoscopic or open procedures on the colon/rectum were performed between the 1st of January 2002 and the 31st of December 2002. 74% were treated by a laparoscopic and 26% by an open approach. 10 out of 103 patients did not undergo a colonic resection but instead an emergency colostomy/ ileostomy or oversewing of a bowel leak, in 8 cases performed laparoscopically. 44 patients have been operated for a benign disease (36 laparoscopic and 8 open procedures) and 59 patients have been treated for a malignant disease (40 laparoscopic and 19 open procedures). The average operating time for the laparoscopic resection was 160 minutes in comparison to 182 minutes for the open resection. The conversion rate (inclusive of non-resection procedures) was 5% for a benign disease and 11% for colorectal cancer. The minor complication rate was 16% in laparoscopic surgery and 30% in open surgery. We saw two major complications in both the open and laparoscopic groups (4%). Reoperation was necessary in one patient out of 103. The average postoperative hospital stay was 7.78 days for the laparoscopic and 16.6 days for the open group. The hospital mortality was 2.9%. CONCLUSION: The laparoscopic colorectal resection is a safe and beneficial procedure for the patient when used in experienced hands.

Colonic Neoplasms↗

PubMed2002

Oxygen-limited thermal tolerance in Antarctic fish investigated by MRI and (31)P-MRS.

The hypothesis of an oxygen-limited thermal tolerance was tested in the Antarctic teleost Pachycara brachycephalum. With the use of flow-through respirometry, in vivo (31)P-NMR spectroscopy, and MRI, we studied energy metabolism, intracellular pH (pH(i)), blood flow, and oxygenation between 0 and 13 degrees C under normoxia (PO(2): 20.3 to 21.3 kPa) and hyperoxia (PO(2): 45 kPa). Hyperoxia reduced the metabolic increment and the rise in arterial blood flow observed under normoxia. The normoxic increase of blood flow leveled off beyond 7 degrees C, indicating a cardiovascular capacity limitation. Ventilatory effort displayed an exponential rise in both groups. In the liver, blood oxygenation increased, whereas in white muscle it remained unaltered (normoxia) or declined (hyperoxia). In both groups, the slope of pH(i) changes followed the alpha-stat pattern below 6 degrees C, whereas it decreased above. In conclusion, aerobic scope declines around 6 degrees C under normoxia, marking the pejus temperature. By reducing circulatory costs, hyperoxia improves aerobic scope but is unable to shift the breakpoint in pH regulation or lethal limits. Hyperoxia appears beneficial at sublethal temperatures, but no longer beyond when cellular or molecular functions become disturbed.

Animals↗

PubMed2001

Prevention of human smooth muscle cell proliferation without induction of apoptosis by the topoisomerase I inhibitor topotecan.

Despite significant improvements in the treatment of atherosclerotic disease involving procedures such as angioplasty, bypass grafting, endartherectomy, or stent implantation, secondary failure due to late restenosis still occurs in 30-50% of individuals. Restenosis and later stages of atherosclerotic lesions arise from a complex series of fibroproliferative responses to vascular injury that are triggered by potent growth-regulatory molecules and finally result in vascular smooth muscle cell proliferation, migration, and neointima formation. The aim of this study was to investigate the antiproliferative effects of the topoisomerase I inhibitor topotecan on human arterial coronary smooth muscle cells. Following incubation of cells with different drug concentrations, mitotic indices were measured by bromodeoxyuridine incorporation, while cellular mitochondrial activity was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Continuous incubation with topotecan for 7 days resulted in a complete and dose-dependent reduction of smooth muscle cell proliferation, and topotecan inhibited cell proliferation in the presence of growth factors as well. In contrast, mitochondrial activity was only partially decreased. Remarkably, although even short-term incubations for 20 min were sufficient to induce a long-lasting growth inhibition, topotecan did not induce apoptosis. Our results therefore suggest that, based on its drug profile, the topoisomerase I inhibitor topotecan may be a promising drug to inhibit restenosis occurring after coronary angioplasty with local devices.

Apoptosis↗

PubMed2001

He-Ne laser irradiation protects B-lymphoblasts from UVA-induced DNA damage.

The effect of He-Ne laser (632.8 nm) pre-irradiation on UVA (343 nm)-induced DNA damage in the human B-lymphoblast cell line NC37 was investigated using the comet assay. He-Ne laser pre-irradiation was observed to result in a dose-dependent decrease in UVA-induced DNA damage. This effect was also found to be dependent on the incubation period between He-Ne laser pre-irradiation and the UVA exposure. Whereas the control cells with a higher DNA damage point to an initial ability of faster repair, both the control and the He-Ne laser pre-irradiated cells subsequently show the same rate of DNA repair. The results suggest that He-Ne laser irradiation protect the cells from UVA-induced DNA damage primarily through an influence on processes that prevent an initial DNA damage.

B-Lymphocytes↗

PubMed2001

Simultaneous observations of haemolymph flow and ventilation in marine spider crabs at different temperatures: a flow weighted MRI study.

In vivo magnetic resonance imaging (MRI) and angiography were applied to the marine spider crab Maja squinado for a study of temperature effects and thermal tolerance. Ventilation and haemolymph circulation were investigated during progressive cooling from 12 degrees C to 2 degrees C. The anatomical resolution of MR images from Maja squinado obtained with a standard spin echo sequence were suitable to resolve the structures of various internal organs. The heart of the animal could be depicted without movement artifacts. The use of a flow compensated gradient echo sequence allowed simultaneous observations of ventilation, reflected by water flow through the gill chambers as well as of haemolymph flow. Simultaneous investigation of various arteries was possible by use of flow weighted MRI. In addition to those accessible by standard invasive flow sensitive doppler sensors, flow changes in gill, leg arteries and the venous return could be observed. Both ventilation and haemolymph flow decreased during progressive cooling and changes in haemolymph flow varied between arteries. Haemolymph flow through the Arteria sternalis, some gill and leg arteries was maintained at low temperatures indicating a reduced thermal sensitivity of flow in selected vessels. In support of previous invasive studies of haemolymph flow as well as heart and ventilation rates, the results demonstrate that the operation of gills and the maintenance of locomotor activity are critical for cold tolerance. A shift in haemolymph flow between arteries likely occurs to ensure the functioning of locomotion and ventilation in the cold.

Animals↗

PubMed2000

Resistance to freshwater exposure in White Sea Littorina spp. I: Anaerobic metabolism and energetics.

Anaerobic metabolism and changes in the osmotic concentration of extravisceral fluid were studied in the White Sea periwinkles (Littorina littorea, Littorina saxatilis and Littorina obtusata) during freshwater exposure. Resistance to hypoosmotic stress increased in the order: L. obtusata < L. saxatilis < L. littorea. Our data suggest that osmotic shock is not a primary reason for mortality of the periwinkles under these conditions. During environmental anaerobiosis, considerable succinate accumulation (up to 10(-19) micromol g(-1) wet weight), and depletion of phosphagen and ATP pools were found in the studied species. Other metabolic end products (alanopine, strombine, lactate, acetate or propionate) were not detected. Succinate accumulation and net ATP breakdown were the fastest in the least resistant species, L. obtusata, and slowest in the most resistant, L. littorea. Rate of ATP turnover decreased during freshwater exposure in L. littorea and L. saxatilis, but not in L. obtusata. Our data suggest that differential resistance of three studied Littorina spp. to extreme hypoosmotic stress may be related to their different abilities to reduce metabolic rate and ATP turnover during sustained anoxia. Species-specific variations in anaerobic capacity of Littorina spp. are discussed in relation to their vertical distribution, size and ecology.

Adenosine Diphosphate↗

PubMed2000

Resistance to freshwater exposure in White Sea Littorina spp. II: Acid-base regulation.

Parameters of acid-base and energy status were studied by in vivo 31P-nuclear magnetic resonance spectroscopy in three White Sea Littorina spp. (L. littorea, L. saxatilis and L. obtusata) during prolonged anaerobiosis in freshwater. Intracellular pH decreased significantly, especially during the early period of anaerobiosis, but later the decrease in intracellular pH slowed down considerably, suggesting a capacity for intracellular pH regulation in all three species. There was a trend for intracellular pH to fall most rapidly in the least freshwater-resistant species, L. obtusata, as compared to the most resistant, L. littorea. Non-bicarbonate, non-phosphate buffer values estimated by the homogenate technique were similar in the three studied species (28-37 mmol pH(-1) kg(-1) wet weight) and did not change during freshwater exposure. The CaCO3 buffer value of the foot tissues was considerably higher (171-218 mmol pH(-1) kg(-1) wet weight) and decreased significantly during freshwater exposure. The contribution of the multiple tissue buffering systems to intracellular pH regulation in Littorina spp. shifts between different stages of freshwater exposure. Initially, the non-bicarbonate, non-phosphate tissue buffering system seems to be of major importance for metabolic proton buffering at intracellular pH between 7.5 and 7.0. During later stages of anaerobiosis and at lower intracellular pH, the CaCO3 buffer is involved in proton buffering. Decrease in the CaCO3 buffer value during freshwater exposure was in quantitative agreement with the amount of metabolic protons buffered, thus suggesting that CaCO3 tissue stores may serve as a major buffering system during prolonged anaerobiosis in Littorina spp.

Acid-Base Equilibrium↗

PubMed2000

UV-A breakage sensitivity of human chromosomes as measured by COMET-FISH depends on gene density and not on the chromosome size.

COMET-FISH, a single cell-based combination of COMET-assay (also known as single cell gel electrophoresis (SCGE)) with fluorescence in situ hybridization (FISH) allows region specific studies on DNA stability and damage. COMET-FISH can be used to investigate UV-A-induced DNA damage of selected whole chromosomes. In the present work, a modified COMET-FISH protocol with whole chromosome painting probes was used to study whether UV-A-induced DNA damage is distributed randomly over the whole genome or occurs at preferred sites. The study was performed with 12 different chromosome painting probes (for chromosomes 1, 2, 3, 8, 9, 11, 14, 18, 19, 21, X and Y). The results on human lymphocytes irradiated with 500 kJ/m2 at a wavelength of 365 nm indicate that the induced number of chromatin strand breaks does not correlate with the chromosome size. They therefore are distributed in a non-random manner. For example, fragments of the gene-rich chromosome chromosome 1 were found in the comet tail in only 3% of the examined cells, and thus chromosome 1 is rather stable, whereas fragmentation of the gene-poor chromosome 8 was observed in 25% of all comets. On the basis of all 12 chromosomes analyzed, an inverse correlation between the density of active genes and the sensitivity toward UV-A radiation is found.

Cells, Cultured↗

PubMed2000

Modulation of the cost of pHi regulation during metabolic depression: a (31)P-NMR study in invertebrate (Sipunculus nudus) isolated muscle.

Extracellular acidosis has been demonstrated to play a key role in the process of metabolic depression under long-term environmental stress, exemplified in the marine invertebrate Sipunculus nudus. These findings led to the hypothesis that acid-base regulation is associated with a visible cost depending on the rate and mode of H(+)-equivalent ion exchange. To test this hypothesis, the effects of different ion-transport inhibitors on the rate of pH recovery during hypercapnia, on energy turnover and on steady-state acid-base variables were studied in isolated body wall musculature of the marine worm Sipunculus nudus under control conditions (pHe 7.90) and during steady-state extracellular acidosis (pHe 7.50 or 7.20) by in vivo (31)P-NMR and oxygen consumption analyses. During acute hypercapnia (2 % CO(2)), recovery of pHi was delayed at pHe 7.5 compared with pHe 7.9. Inhibition of the Na(+)/H(+)-exchanger by 5-(N,N-dimethyl)-amiloride (DMA) at pHe 7.5 delayed recovery even further. This effect was much smaller at pHe 7.9. Inhibition of anion exchange by the addition of the transport inhibitor 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) prevented pH recovery at pHe 7.5 and delayed recovery at pHe 7.9, in accordance with an effect on Na(+)-dependent Cl(-)/HCO(3)(-) exchange. The effects of ouabain, DIDS and DMA on metabolic rate were reduced at low pHe, thereby supporting the conclusion that acidosis caused the ATP demand of Na(+)/K(+)-ATPase to fall. This reduction occurred via an inhibiting effect on both Na(+)/H(+)- and Na(+)-dependent Cl(-)/HCO(3)(-) (i.e. Na(+)/H(+)/Cl(-)/HCO(3)(-)) exchange in accordance with a reduction in the ATP demand for acid-base regulation during metabolic depression. Considering the ATP stoichiometries of the two exchangers, metabolic depression may be supported by the predominant use of Na(+)/H(+)/Cl(-)/HCO(3)(-) exchange under conditions of extracellular acidosis.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1999

Mechanism of the sympathoinhibition produced by the clonidine-like drugs rilmenidine and moxonidine.

The mechanism of the sympathoinhibition produced by two new derivatives of clonidine, rilmenidine and moxonidine, was studied. One aim was to determine the receptor responsible for the central sympathoinhibition by these drugs. Rilmenidine and moxonidine were injected into the cisterna cerebellomedullaris. They decreased blood pressure and the plasma noradrenaline concentration. After rilmenidine and moxonidine, two selective alpha 2-adrenoceptor antagonists (devoid of affinity for I1 binding sites), yohimbine and SK&F86466, were given intracisternally. They completely counteracted the hypotensive effects of rilmenidine and moxonidine, indicating that alpha 2-adrenoceptors are involved in the central sympathoinhibition produced by these drugs. The other aim was to determine if peripheral presynaptic inhibition of noradrenaline release from postganglionic sympathetic neurons contributes to the overall reduction of sympathetic tone. Rilmenidine and moxonidine were injected i.v. in pithed rabbits with electrically stimulated sympathetic outflow. They dose-dependently lowered blood pressure and the plasma noradrenaline concentration and inhibited stimulation-evoked cardioacceleration. Moreover, the doses necessary for these peripheral effects were identical to the doses that reduce the sympathetic nerve firing rate and blood pressure in conscious rabbits. These observations indicate that peripheral presynaptic inhibition of noradrenaline release from postganglionic sympathetic neurons contributes to the overall reduction of sympathetic tone produced by rilmenidine and moxonidine in intact animals.

Adrenergic alpha-Agonists↗

PubMed1999

Identification by microscopically controlled comet assay of peritoneal macrophages in a mixture of peritoneal exudate for DNA strand break analysis.

A simple modification of the alkaline comet assay allows the study of DNA damage in a specific cell type in a mixture of primary cells. Peritoneal macrophages from mice are selected from other peritoneal exudate cells without complex preparation and separation steps by their size and shape of the nuclei and their comets. The DNA damage can be well characterised by the manually monitored parameter 'tail length'. Complex measurement of the 'tail moment', often used for characterising DNA damage is not required, a fact which further simplifies the protocol. The distribution of tail length within one sample is symmetric and can be described by a Gaussian distribution and the mean tail length. As a first application, UV-A sensitivity of resident and stimulated macrophages was studied. The resident macrophages were more sensitive to UV-A than the stimulated ones. DNA damage repair follows the same simple monoexponential time course for both cell types. The simplicity of results, i.e., applicability of tail lengths and Gaussian statistics as well as monoexponential kinetics, suggest that microscopically controlled comet assay is well suited to study elementary processes of DNA damage induction and repair.

Animals↗

PubMed1999

Simultaneous recording of evoked potentials and T2*-weighted MR images during somatosensory stimulation of rat.

Somatosensory evoked potentials (SEP) and T2*-weighted nuclear magnetic resonance (NMR) images were recorded simultaneously during somatosensory stimulation of rat to investigate the relationship between electrical activation of the brain tissue and the signal intensity change in functional NMR imaging. Electrical forepaw stimulation was performed in Wistar rats anesthetized with alpha-chloralose. SEPs were recorded with calomel electrodes at stimulation frequencies of 1.5, 3, 4.5, and 6 Hz. At the same time, T2*-weighted imaging was performed, and the signal intensity increase during stimulation was correlated with the mean amplitude of the SEP. Both the stimulation-evoked signal intensity increase in T2*-weighted images and the amplitude of SEPs were dependent on the stimulation frequency, with the largest signals at a stimulation frequency of 1.5 Hz and decreasing activations with increasing frequencies. The feasibility of simultaneous, artifact-free recordings of T2*-weighted NMR images and of evoked potentials is proved. Furthermore, the study demonstrates-in the intact brain-the validity of functional magnetic resonance imaging for estimating the intensity of electrocortical activation.

Animals↗

PubMed1999

Analysis of the receptor involved in the central hypotensive effect of rilmenidine and moxonidine.

The aim of this study was to determine whether alpha2-adrenoceptors or imidazoline I1-receptors are responsible for the central sympathoinhibition produced by rilmenidine and moxonidine, two clonidine-like antihypertensive drugs. Rilmenidine and moxonidine were compared with the indirectly acting alpha2-adrenoceptor agonist alpha-methyldopa. Three antagonists were used. Yohimbine and SK&F86466 were used as selective alpha2-adrenoceptor antagonists. They were compared with efaroxan which is also an alpha2-adrenoceptor antagonist, but, in addition, possesses affinity for imidazoline I1-receptors. According to some but not all studies, the affinity of efaroxan for I1-receptors is much higher than its affinity for alpha2-adrenoceptors. Drugs were administered into the cisterna cerebellomedullaris of conscious rabbits by a catheter implanted previously under halothane anaesthesia. Rilmenidine (10 microg kg(-1)), moxonidine (0.3 microg kg(-1)) and alpha-methyldopa (0.4 mg kg(-1)) lowered blood pressure and the plasma noradrenaline concentration; the degree of sympathoinhibition produced by the three agonists was very similar. When injected after the agonists, efaroxan (0.1-14 microg kg(-1); cumulative doses), yohimbine (0.4-14 microg kg(-1)) and SK&F86466 (0.4-44 microg kg(-1)) counteracted the effects of the agonists on blood pressure and the plasma noradrenaline concentration. Efaroxan was about tenfold more potent than yohimbine and SK&F86466 at antagonizing the hypotensive effects of alpha-methyldopa. Similarly, efaroxan was two- to tenfold more potent than yohimbine and SK&F86466 against rilmenidine and moxonidine. Finally, efaroxan was about as potent against alpha-methyldopa as against rilmenidine and moxonidine. The results confirm previous observations that selective alpha2-adrenoceptor antagonists are capable of completely antagonizing effects of rilmenidine and moxonidine. The effects of the alpha2-adrenoceptor antagonist with an additional high affinity for imidazoline I1-receptors, efaroxan, can also be explained by blockade of alpha2-adrenoceptors. Efaroxan was more potent against rilmenidine and moxonidine than the selective alpha2-adrenoceptor antagonists. This was probably due to the fact that the affinity of efaroxan for alpha2-adrenoceptors is higher than the affinity of yohimbine and SK&F86466, since efaroxan was also the most potent of the three antagonists against the indirectly acting alpha2adrenoceptor agonist alpha-methyldopa. The observation that efaroxan was equally potent against rilmenidine and moxonidine and against alpha-methyldopa suggests that the same receptors were involved in the effects of the three agonists, alpha2-adrenoceptors; this observation is not compatible with the high I1/alpha2 selectivity of efaroxan and the hypothesis that rilmenidine and moxonidine activate I1-receptors, whereas alpha-methyldopa activates alpha2-adrenoceptors. Thus, the data do not indicate involvement of I1 imidazoline receptors in the central sympathoinhibition elicited by rilmenidine and moxonidine in rabbits. It is likely that rilmenidine and moxonidine produce sympathoinhibition by activating the same receptors which are activated by the indirectly acting catecholamine alpha-methyldopa, namely alpha2-adrenoceptors.

Adrenergic alpha-Agonists↗