共查询到20条相似文献,搜索用时 15 毫秒
1.
S F Hipkins 《The Journal of experimental zoology》1985,235(1):7-20
Heart output, arterial pressures, and heart rate were measured directly in conscious unrestrained eels (Anguilla australis) and responses to intra-arterial injection of adrenaline monitored. Adrenaline increased systemic vascular resistance, heart output, and cardiac stroke volume in all animals. In some cases small transient decreases in stroke volume and hence heart output were seen at the peak of the pressor response: These probably reflect a passive decrease in systolic emptying due to increased afterload on the heart. In most cases, adrenaline produced tachycardia; but two animals showed consistent and profound reflex bradycardia, which was accompanied by a concomitant increase in stroke volume such that heart output was maintained or increased slightly. The interaction of changes in heart output and systemic vascular resistance produced complex and variable changes in arterial pressure. There was no consistent pattern of changes in branchial vascular resistance. Atropine treatment in vivo revealed vagal cardio-inhibitory tone in some animals and always blocked the reflex bradycardia seen during adrenaline induced hypertension. In some animals, adrenaline injection after atropine pretreatment led to the establishment of cyclic changes in arterial pressure with a period of about 1 min (Mayer waves). 相似文献
2.
Knut Pettersson Stefan Nilsson 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1980,137(2):131-138
Summary Ventral (VAP) and dorsal (DAP) aortic blood pressure, heart rate (HR) and cardiac output (
) were recorded simultaneously in unanaesthetized Atlantic cod, and the effects of vasoactive drugs on the cardio-vascular parameters studied. Mean resting values for the parameters were VAP=4,39 kPa, DAP=2,49 kPa, HR=41 beats/min, and
= 29,1 ml/min×kg. Adrenaline constricted the systemic vasculature, dilated the branchial vasculature and caused a decrease of HR and
due to a cholinergic reflex. After atropine pre-treatment this reflex was abolished, and the effect of adrenaline on blood pressure enhanced. A small decrease in
persisted after atropine, presumably reflecting the effect of an increased end-systolic afterload.Phenylephrine produced a weak increase in systemic vascular resistance, while isoprenaline lowered both systemic and branchial vascular resistance. The effect of isoprenaline is probably mediated by beta adrenoceptors in both vascular beds, since propranolol antagonizes the effect.Acetylcholine in low doses produces a drop in
without affecting HR, while higher doses also stop the heart. There is no significant change in either branchial and systemic vascular resistance after acetylcholine.Abbreviations
VAP
mean ventral aortic blood pressure
-
DAP
mean dorsal aortic blood pressure
-
TBPD
trans-branchial blood pressure drop
-
HR
heart rate
-
SV
stroke volume
-
cardiac output (ventral aortic blood flow)
-
VR
g
branchial vascular resistance
-
VR
s
systemic vascular resistance 相似文献
3.
Rocha ML Rantin FT Kalinin AL 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2007,177(7):713-721
Experiments were carried out to investigate the heart rate of Synbranchus marmoratus after changing the temperature of the water contained in the experimental chamber of the acclimated fish (from 25 to 35°C
and from 25 to 15°C). Then, an isometric cardiac muscle preparation was used to test the relative importance of Ca2+ released from the sarcoplasmic reticulum and Ca2+ influx across the sarcolemma for the cardiac performance under different thermal conditions: 25°C (acclimation temperature),
15 and 35°C. Adrenaline and ryanodine were used to modulate the Ca2+ flux through the sarcolemma and the sarcoplasmic reticulum, respectively. Ryanodine reduced the peak tension by approximately
47% at 25°C, and by 53% at 35°C; however, it had no effect at 15°C. A high adrenaline concentration was able to ameliorate
the negative effects of ryanodine. Despite increasing the peak tension, adrenaline increased the times necessary for contraction
and relaxation. We conclude that the sarcoplasmic reticulum is active in contributing Ca2+ to the development of tension at physiological contraction frequencies. The adrenaline-stimulated Ca2+ influx is able to increase the peak tension, even after addition of ryanodine, at physiologically relevant temperatures and
pacing frequencies. 相似文献
4.
In-vivo quantification of loads in the constitutive structures of the osteoarthritic knee can provide clinical insight, particularly when planning a surgery like the opening-wedge high tibial osteotomy (HTO). A computational knee model was created to estimate internal kinetics during walking gait. An optimization approach partitioned loads between the muscles, ligaments, medial and lateral contact surfaces of the tibial–femoral joint. Three kinetic measures were examined in 30 HTO patients: external knee adduction moment (EKAM), medial compartment load (ML) and the medial-to-lateral compartment loads ratio (MLR). Three time points were compared: immediately pre-HTO, 6 and 12 months post-HTO. Three hypotheses were tested: (1) HTO reduces an EKAM, an ML and an MLR, (2) these measures are not significantly different at 6 and 12 months post-HTO, and (3) the change in the impulse of EKAM due to a HTO is well-correlated with the impulse of an MLR.The three hypotheses were confirmed. First peak of an EKAM during stance phase was reduced significantly by 1.70% BW-ht. ML and MLR at the same instance were reduced significantly by 0.56%BW and 1.0, respectively. These measures were not significantly different between 6 and 12 months post-HTO. Changes in impulse of an EKAM and an MLR were moderately well-correlated between the pre-HTO and 6 months post-HTO time points (R2=0.5485). Therefore, the external measure EKAM-impulse is a good proxy of the internal kinetic measure of an MLR-impulse, explaining about 55% of the variance in the change due to a HTO intervention. 相似文献
5.
Contribution of Na+ and membrane depolarization to contraction induced by adrenaline in the guinea pig vas deferens 总被引:2,自引:0,他引:2
S Usune T Katsuragi Y Sakamoto T Furukawa 《Canadian journal of physiology and pharmacology》1986,64(6):720-723
The contribution of Na+ and membrane depolarization to biphasic contractions induced by adrenaline were investigated in the smooth muscle of guinea pig vas deferens. Adrenaline (5 X 10(-6) M) produced an initial small contraction (first contraction) followed by a large tonic contraction (second contraction) with subsequent rhythmic activity. The entire response to adrenaline was largely inhibited by phentolamine (5 X 10(-6) M). By adding an appropriate concentration of Mn2+ (2 X 10(-4) M) or nifedipine (3 X 10(-7) M), a Ca2+ blocker, the second contraction was strongly reduced, accompanied by abolishment of the rhythmic contraction, whereas the first contraction was virtually unaffected. However, the first contraction was markedly suppressed by a higher concentration of Mn2+. All contractions produced by adrenaline were greatly reduced in Ca2+-free solution containing 0.5 mM EGTA. By lowering external Na+ concentration, the first contraction was markedly increased without greatly affecting the second contraction. By exposure to Na+-free isotonic high K+ solution, which elicited a greater depolarization of the membrane, the first contraction produced by adrenaline was also greatly potentiated, while the second and rhythmic contractions were eliminated. These results suggest that the adrenaline-evoked first contraction may be due to an influx of membrane bound Ca2+ which is independent of membrane depolarization, while the second (rhythmic) contraction is due to an influx of extracellular Ca2+ which is dependent upon depolarization. 相似文献
6.
R. M. Bevan P. J. Butler 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1994,164(5):349-354
Arterial blood pressure was monitored in voluntarily diving tufted ducks. Mean arterial blood pressure while diving increased during the pre-dive tachycardia, fell to resting levels on submersion, then gradually increased before peaking on surfacing. Estimated total peripheral resistance fell during the pre-dive and post-dive tachycardia, presumably to allow the oxygen stores to be loaded and replenished respectively and/or for carbon dioxide levels to be reduced. Changes in mean arterial blood pressure and total peripheral resistance suggest that peripheral vasoconstriction occurs in some vascular beds during a dive. An increase in arterial blood pressure (and therefore perfusion pressure) may be employed to increase blood flow and oxygen delivery to the active leg muscles.Abbreviations ecg
Electrocardiogram, f
H, heart rate
- MABP
mean arterial blood pressure
-
P
b
blood pressure(s)
- TPR
total peripheral resistance
-
V
b
cardiac output 相似文献
7.
Characterization of Low pH-induced Catecholamine Secretion in the Rat Adrenal Medulla 总被引:1,自引:0,他引:1
Abstract: Catecholamine (CA) secretion was evoked when the isolated rat adrenal gland was perfused with HEPES-buffered Krebs solution acidified by the addition of HCI or by gassing with 95% O2/5% CO2. The secretion was detectable at pH 7.0 and increased with decreasing pH until at ~6.4. The low pH-induced CA secretion consisted of two phases, an initial transient response followed by a sustained phase. An intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(N,N-diethylamino)octyl ester, selectively inhibited the initial phase of secretion. Both of the responses were resistant to nifedipine, a blocker of voltage-gated Ca2+ channel, but were completely inhibited in Ca2+-free (1 mM EGTA containing) solution. Adrenaline was an exclusive component in CAs released by low pH. The time course and extent of intracellular acidification caused either by low pH in the external medium or by the offset of a transitory NH4CI application had no correlation with those of the secretory responses in the corresponding period. These results suggest that extracellular acidification preferentially activates adrenaline secretive cells to evoke CA secretion and that this low pH-induced CA secretion may be mediated by dihydropyridine-insensitive Ca2+ influx. Furthermore, the initial transient phase of the low pH-induced CA secretion might be caused by a Ca2+ release from intracellular stores, which is also induced by the Ca2+ influx. 相似文献
8.
E. Gardaire M. Avella J. Isaia M. Bornancin 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1991,161(3):265-269
Summary Using the isolated-perfused head preparation at a constant flow rate, hemodynamic effects of adrenaline were studied in trout gills. The calculation of the vascular spaces was performed with the isotopic pulse technique allowing measurement of the distribution space of the tracer.The results show that the branchial arterial circuit was cleared more quickly than the branchial venous and cephalic circuits. Adrenaline addition significantly increased the volume of the branchial arterial circuit at the expense of the venous circuit, illustrating the closing of arterio-venous sphincters under catecholamine control. The increase of the arterial volume could be explained by a vasodilation of the arterial circuit, rather than resulting from lamellar recruitment. Furthermore, the flow rate of the cephalic circuit represented 5% of the total branchial flow rate.Abbreviations
dpm
radioactive decay per minute
-
F
flow rate
-
HSA
human serum albumin
-
T
1/2
half-time clearance
-
V
distribution space 相似文献
9.
The addition of 200 nM asialo-orosomucoid to isolated rat hepatocytes caused a temporary reduction (down to 20% of control values) in the rate of influx of 45Ca2+ ions in the cells. After 5 min the rate of influx gradually returned to control values. The change in influx rates was dose-dependent. The rate of efflux of calcium ions from cells previously loaded with 45Ca2+ was reduced by 20%. Asialo-fetuin had qualitatively the same effect as asialo-orosomucoid; native fetuin produced no changes. 相似文献
10.
The addition of 200 nM asialo-orosomucoid to isolated rat hepatocytes caused a temporary reduction (down to 20% of control values) in the rate of influx of 45Ca2+ ions in the cells. After 5 min the rate of influx gradually returned to control values. The change in influx rates was dose-dependent. The rate of efflux of calcium ions from cells previously loaded with 45Ca2+ was reduced by 20%. Asialo-fetuin had qualitatively the same effect as asialo-orosomucoid; native fetuin produced no changes. 相似文献
11.
J.-J. Janvier M. Peyraud-Waïtzenegger P. Soulier 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1996,166(2):131-137
The effects of serotonin on continuously recorded cardiac parameters (heart rate, cardiac output, cardiac stroke volume), ventral and dorsal aortic blood pressures, branchial and systemic vascular resistances were investigated in the European eel in vivo. Intravenous administration of serotonin (30 g · kg–1) caused a marked bradycardia (45%) and a simultaneous decrease in cardiac output (50%), ventral (35%) and dorsal (50%) aortic blood pressures. Branchial resistance was markedly increased (60%) and systemic resistance decreased (30%). Cardiac stroke volume remained unchanged. The effects of serotonin on cardiac mained unchanged. The effects of serotonin on cardiac parameters were suppressed either by methysergide or a bilateral section of the cardiac vagus. Bradycardia could then be regarded as the consequence of a vagal mechanism triggered by serotonin action on central methysergide-sensitive serotonergic receptors. No inotropic effect of serotonin was observed. This lack of myocardiac contractility modification is discussed. The serotonin-mediated branchial vasoconstriction was attenuated by vagotomy, whereas the residual increase in branchial resistance (40%) was suppressed by methysergide. The serotonin-mediated branchial vasoconstriction could be the consequence of both a passive mechanism (compliance) caused by the decrease in cardiac output and an active mechanism involving methysergide-sensitive serotonergic receptors of the branchial vasculature. A possible involvement of this vasomotor effect in gill oxygen uptake is discussed. The serotonin-induced systemic vasodilation was insensitive either to cardiac vagotomy or to 5-HT1/2, 5-HT3 and 5-HT4 receptor antagonists, suggesting the involvement of a local mechanism which remains to be assessed.Abbreviations
CSV
cardiac stroke volume
-
DAP
dorsal aortic pressure
-
HR
heart rate
-
QC
cardiac output
-
VAP
ventral aortic pressure
-
VR
b
branchial vascular resistance
-
VR
s
systemic vascular resistance
-
VR
t
total vascular resistance
- 5-HT
5-Hydroxytryptamine serotonin
- RBI
Research Biochemical Incorporated, metoclopramide HCl 相似文献
12.
H. Y. Xu K. R. Olson 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1993,163(6):470-476
The importance of neuronal and lumenal vascular adrenoceptors in the regulation of vascular reactivity was examined in rainbow trout (Oncorhynchus mykiss), in vivo and in vitro. In vivo, ganglionic blockade with hexamethonium or -adrenoceptor blockade, with either phentolamine or prazosin, produced similar (7 mmHg) decreases in dorsal aortic blood pressure. The drop in dorsal aortic pressure produced by phentolamine or prazosin was due to reduced systemic vascular resistance. Neither the -adrenoceptor antagonist, phenoxybenzamine nor chemical sympathectomy with 6-hydroxy-dopamine affected dorsal aortic pressure. However, after chemical sympathectomy, phenoxybenzamine lowered dorsal aortic pressure to levels similar to that produced by either phentolamine or prazosin. Plasma epinephrine and norepinephrine concentrations increased four- and twofold, respectively, in sympathectomized fish. Sympathectomy also produced a leftward shift in the epinephrine dose/response curve of the in vitro perfused splanchnic vasculature, placing the effective catecholamine concentration well within the in vivo plasma levels. These results indicate that following chemical sympathectomy arterial blood pressure is stabilized by circulating catecholamines through the combined effect of increased plasma catecholamine concentrations and increased sensitivity of vascular adrenoceptors. Phenoxybenzamine is incapable of blocking neuronal vascular adrenoceptors but is a potent antagonist of the up-regulated adrenoceptors, suggesting that the latter are localized on the lumenal side of the vessel.Abbreviations 6OH-DA
6-hydroxy dopamine
-
EC
50
half-maximal response
- EDTA
ethylenediaminetetra-acetate
- PE
polyethylene
- PBS
phosphate-buffered saline
-
P
da
dorsal aortic pressure
- USP
United States Pharmacopeia 相似文献
13.
Summary
Salicornia fruticosa was collected from a salt marsh on the Mediterranean sea coast in Libya. Growth and gas exchange of this C3 species were monitered in plants pretreated at various NaCl concentrations (0, 171, 342, 513 and 855 mM). Maximum growth was at 171 mM NaCl under cool growth conditions (20/10° C) and at 342 mM NaCl under warm growth conditions (30/15° C) with minimum growth at 0 mM NaCl (control). Net photosynthesis (Pn) was greatest in plants grown in 171 mM NaCl with plants grown at 513 and 855 mM having lowest rates. Maximum Pn was at 20–25° C shoot temperatures with statistically significant reductions at 30° C in control plants while salt treated plants showed such reductions at 35° C. Salt treatments increased dark respiration over the control at 171 and 342 mM but reduced it at higher concentrations. Photorespiration was reduced by salt treatment and increased by increasing shoot temperature. Greatest transpiration was in 171 mM NaCl treated plants and increasing shoot temperature increased transpiration in all treatments. Stomatal resistance to CO2 influx was influenced only moderately by temperature while increasing salinity resulted in increased stomatal resistance. In general both temperature and salinity increased the mesophyll resistance to CO2 influx. The species seems adapted to the warm saline habitat along the Mediterranean sea coast, at least partially, by its ability to maintain relatively high Pn at moderate NaCl concentrations over a broad range of shoot temperatures. 相似文献
14.
Identification of phloem sieve elements as the site of resistance to silverleaf whitefly in resistant alfalfa genotypes 总被引:1,自引:0,他引:1
Experiments were conducted to locate the plant tissue where resistance is expressed against silverleaf whitefly, Bemisia argentifolii Bellows and Perring (Homoptera: Aleyrodidae), in alfalfa, Medicago sativa L. (Fabaceae), genotypes previously shown to have high levels of resistance against this pest. Previous work demonstrated that resistance in the resistant alfalfa genotypes was expressed primarily as high first‐instar mortality; consequently this study focused on first‐instar nymphs. Examination of stylets in cleared leaf tissue indicated that first‐instar nymphs located vascular bundles with equal success on resistant and susceptible alfalfa genotypes. Furthermore, direct current electrical penetration graphs (DC‐EPG) indicated that sieve elements were penetrated and phloem ingestion behavior was initiated with equal success on resistant and susceptible genotypes. Thus, the mechanism of resistance does not reside in tissues encountered by the stylets prior to penetrating a phloem sieve element. Honeydew production (as a proxy for ingestion) was greatly reduced on two resistant genotypes compared to the two susceptible genotypes. The frequency distribution of honeydew production was bimodal, indicating that most individuals on the resistant genotypes produced little or no honeydew while some produced as much honeydew as whiteflies on the susceptible genotypes. This indicates that expression of resistance is an all‐or‐nothing phenomenon; an individual nymph either encounters resistance and cannot sustain ingestion or it does not encounter resistance and ingests just as well as on a susceptible plant. Intermediates are rare. DC‐EPGs indicate that phloem ingestion behavior is significantly reduced on two of the resistant genotypes compared to the susceptible genotypes. The primary reason for this appears to be more frequent termination of phloem ingestion behavior on at least one of the resistant genotypes. On one of the resistant genotypes, the productivity of EPG‐measured phloem ingestion behavior (honeydew produced per min of phloem ingestion behavior) was reduced compared to a susceptible control. 相似文献
15.
We studied the role of plant vascular architecture in the determination of the spatial extent of herbivore induced responses within Betula pendula Roth saplings. The induced responses were measured in bioassays in terms of the relative growth rate of larvae of a geometrid moth, Epirrita autumnata. We hypothesised that the level of induced resistance of a certain leaf would be determined by the degree of vascular connectivity between the leaf in question and a damaged leaf, as suggested by recent theoretical and empirical studies. A comparison of the control plants with the damaged plants indicated that damaging one leaf of a sapling was sufficient to induce an increase in the resistance level. There were also differences among the leaves within a plant in the resistance level, but these differences could not be explained by the degree of vascular connectivity with the damaged leaf. These results suggest that the vascular connections have low power as explanations of the spread and spatial extent of the induced resistance in Betula pendula saplings Instead, the resistance level of all leaves within a sapling increased following the damage. We suggest that the pattern of increased resistance observed in this experiment may be beneficial for the young saplings studied. For young saplings at their early stages of development, it may be beneficial to be able to distribute the induction signal to all leaves as fast as possible and thus repel the herbivore totally. For a young sapling, the capability of repelling the herbivore totally might thus be a feasible strategy whereas an older sapling may tolerate localised damage better and compensate for the damage within the undamaged plant parts. 相似文献
16.
《Mutation Research Letters》1994,323(1-2):53-61
Tritriated water (HTO) is a major toxic effluent from the nuclear power industry, that is released into the environment in large quantities. The low dose radiation effect and dose rate effect of HTO on human lymphocytes and bone marrow cells have not been well studied. The present study was therefore undertaken to investigate the HTO dose-response relationship for chromosomal aberrations in human lymphocytes and bone marrow cells at low in vitro radiation doses ranging from 0.1 to 1 Gy. Lymphocytes (G0 stage) and bone marrow cells were incubated for 10–150 min with HTO at a dose rate of 2cGy/min (555 MBq/ml). The relative biological effectiveness (RBE) of HTO was calculated with respect to 60Co γ-rays for the induction of dicentric and centric ring chromosomes at low radiation doses. The RBE value for HTO β-rays relative to 60Co γ-rays was 2.7 for lymphocytes and 3.1 for chromatid aberrations in bone marrow cells. Lymphocytes were also chronically exposed to HTO for 6.7–80 h at dose rates of 0.5 cGy/min (138.5 MBq/ml) and 0.02 cGy/min (5.6 MBq/ml). There was a 71.5% decrease in the yield of dicentrics and centric rings at the dose rate of 0.02 cGy/min, indicating a clear dose rate effect of HTO. The RBE value for HTO relative to 137Cs γ-rays was 2.0 at a dose rate of 0.02 cGy/min, suggesting that low HTO dose rates produce no increase of the RBE values and that the values may be constant between 2 and 3 within these dose rates. These results should prove useful in assessment of the health risk for humans exposed to low levels of HTO. 相似文献
17.
B. Sarkadi A. Tordai L. Homolya O. Scharff G. Gárdos 《The Journal of membrane biology》1991,123(1):9-21
Summary Jurkat and MOLT-4 cultured T lymphoblasts were loaded with low concentrations (30–50 m) of indo-1 and with high concentrations (3.5–4.5mm) of quin-2, respectively, in order to follow the activation of calcium transport pathways after stimulation of the cells by a monoclonal antibody against the T cell antigen receptor (aCD3), or after the addition of thapsigargin, a presumed inhibitor of endoplasmic reticulum calcium pump. In the indo-1 loaded cells the dynamics of the intracellular calcium release and the calcium influx could be studied, while in the quin-2 overloaded cells the changes in cytoplasmic free calcium concentration ([Ca2+]
i
) were strongly buffered and the rate of calcium influx could be quantitatively determined. We found that in Jurkat lymphoblasts, in the absence of external calcium, both aCD3 and thapsigargin induced a rapid calcium release from internal stores, while upon the readdition of external calcium an increased rate of calcium influx could be observed in both cases, aCD3 and thapsigargin released calcium from the same intracellular pools. The calcium influx induced by either agent was of similar magnitude and had a nonadditive character if the two agents were applied simultaneously. As demonstrated in quin-2 overloaded cells, a significant initial rise in [Ca2+]
i
or a pronounced depletion of internal calcium pools was not required to obtain a rapid calcium influx. The activation of protein kinase C by phorbol ester abolished the internal calcium release and the calcium influx induced by aCD3, while having only a small effect on these phenomena when evoked by thapsigargin. Membrane depolarization by gramicidin inhibited the rapid calcium influx in both aCD3- and thapsigargin-treated cells, although it did not affect the internal calcium release produced by either agent. In MOLT-4 cells, which have no functioning antigen receptors, aCD3 was ineffective in inducing a calcium signal, while thapsigargin produced similar internal calcium release and external calcium influx to those observed in Jurkat cells. 相似文献
18.
19.
Submandibular secretory and vascular responses to stimulation of the parasympathetic innervation and the output of vasoactive intestinal peptide (VIP) were investigated in anaesthetized sheep in the presence and absence of atropine (>/=0.5 mg/kg). In the absence of atropine, parasympathetic stimulation caused an increase in the flow of saliva and a decrease in submandibular vascular resistance; the latter response persisted after the administration of atropine and was then significantly reduced at the lowest but not at the higher frequencies tested. The output of VIP from the gland was frequency dependent over the range of 10-20 Hz (continuously) and significantly increased after atropine (P < 0.02). Furthermore, the fall in vascular resistance was linearly related to log VIP output after total muscarinic blockade. Intracarotid infusions of synthetic VIP produced dose-dependent falls in submandibular vascular resistance, together with a corresponding increase in submandibular blood flow. It is concluded that the atropine-resistant vasodilatation that occurs in this gland during parasympathetic stimulation is likely to be due largely, if not entirely, to the release of VIP. 相似文献
20.
Buss I Garmann D Galanski M Weber G Kalayda GV Keppler BK Jaehde U 《Journal of inorganic biochemistry》2011,105(5):709-717
Decreased influx represents one of the major resistance mechanisms of platinum complexes. In order to address the question if this mechanism of resistance can be overcome by enhancing the lipophilicity of platinum complexes, we investigated the influence of lipophilicity on cellular accumulation and cytotoxicity in a panel of oxaliplatin analogues with different carrier ligands. Cellular accumulation, DNA platination and cytotoxicity were measured in a cisplatin-sensitive and -resistant ovarian carcinoma (A2780/A2780cis) and in an oxaliplatin-sensitive and -resistant ileocecal colorectal adenocarcinoma (HCT-8/HCT-8ox) cell line pair. Platinum concentrations were determined by flameless atomic absorption spectrometry or adsorptive stripping voltammetry. Passive diffusion represented the main influx mechanism of oxaliplatin analogues during the first minutes of incubation as indicated by a correlation between lipophilicity and early influx rate. Afterwards, the predominant influx mechanism was lipophilicity-independent. More lipophilic complexes showed a reduced cytotoxic activity, although the early influx rate was increased. The resistance profiles of the two cell line pairs were found to be different: HCT-8ox cells were less resistant against more lipophilic complexes, whereas A2780cis cells exhibited a comparable degree of resistance against all investigated compounds. However, the reduction in resistance factor of HCT-8ox cells cannot be explained by increased influx suggesting that other resistance mechanisms are circumvented upon exposure to more lipophilic compounds. Though resistance against more lipophilic platinum complexes analogues is lower we conclude that enhancing lipophilicity is not a successful strategy to overcome platinum resistance as higher lipophilicity is also associated with lower cytotoxic activity. 相似文献