ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00811.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

This study explored some toxicological aspects of vanadyl sulphate (VOSO4) treatment of rats made diabetic with a single intravenous injection of streptozotocin (60 mg/kg). Administered in drinking water (0.25, 0.5, 0.75 or 1 mg of VOSO4, 5H2O ml) VOSO4treatment partially or totally corrected some of the alterations associated with the diabetic state (hyperglycaemia, polydipsia, polyphagia, high cholesterol and triglycerides levels) and did not produce any changes in various plasma or blood cell paramenters which were not previously altered by diabetes. Measurement of vanadium levels indicated that tissues accumulated vanadium in the following order of concentrations: bone>kidney>spleen>liver>lung>heart ≥ muscle>blood. Histopathological studies did not reveal any difference in liver, stomach, ileum, spleen, heart and lung from control, non‐treated diabetic or VOSO4‐treated diabetic animals. Kidneys of all non‐treated diabetic animals showed an epithelial cellular swelling of distal tubules while only 2 of 6 VOSO4‐treated diabetic animals showed this alteration. Cellular degeneration of pancreas B‐cells was less marked in VOSO4‐treated that in non‐treated diabetic animals. The study indicates that VOSO4may be a potential ant

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00812.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Irindalone is a new antihypertensive agent with affinity to serotonin (5‐HT2) receptors and at higher concentrations also to α1‐adrenoceptors. The present study was designed to evaluate the relative importance of the antagonism of central and peripheral α1‐ and 5‐HT2‐receptors in the blood pressure lowering properties or irindalone after acute administration. In conscious Sprague‐Dawley rats intravenous irindalone (0.05–1.5 mg/kg) dose‐dependently reduced the blood pressure. In the same dose‐range irindalone antagonized pressor responses to phenylephrine and electrical stimulation of the spinal sympathetic outflow (SNS) in the pithed rats, indicating that the acute blood pressure lowering effect is primarily related to the blockade of α1‐adrenoceptors. However, the concomitant 5‐HT2‐receptor blockade may contribute since irindalone in a dose (0.15 mg/kg) where it had no α‐adrenoceptor blocking properties enhanced the hypotensive response to selective a α1‐adrenoceptor blockade by prazosin (1 μg/kg). We found no evidence that central mechanisms contributed to the blood pressure lowering effect of irindalone. In anaesthetized rats irindalone (1 mg/kg) did not reduce the directly recorded sympathetic nerve activity. Intracerebroventricular administration of irindalone in conscious rats (10–100 μg) had no consistent effects on the blood pressure and did not enhance the hypotensive response to intracerebroventricularly administered prazosin (10 μg). Finally, the hypotensive response to irindalone was not influenced by depletion of central serotonin stores (by PCPA). It is concluded that the blood pressure lowering effect of irindalone following acute administration is related primarily to blockade of peripheral α‐adrenoceptors but that the concomitant bl

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00813.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

This study examined the effect of Oriental hornet venom sac extract (VSE) on the rate of local blood flow in the cerebral cortex of rats. Sublethal doses of VSE in isotonic saline solution were injected into the femoral vein of anaesthetised rats and the rate of blood flow was assessed by the hydrogen clearance technique both before the envenomation as well as during the following 150 min. The injection of VSE was found to induce a prolonged elevation of blood flow in the cerebral cortex. The time of occurrence of this elevation varied in different rats and so also the intensity of the elevation, ranging between 47–212% of the basal values. No exceptional or toxic phenomena were recorded in the course of this investigation. It would seem that the factor(s) responsible for boosting the blood flow is probably one or more of the water soluble components of the hornet veno

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00814.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The anticancer drug hydroxyurea (HU) at doses of 300–800 mg/kg/day causes a dramatic lethality (up to 100% after a 5‐day treatment) in hypophysectomized as well as in adrenalectomized rats drinking physiological saline+ 5% glucose. Mortality in controls was less than 10% over a 5‐day period. Adrenal stimulatory or replacement therapies protect pituitary‐ or adrenal‐ablated rats against HU toxicity. They also counteract white blood cell changes induced by the drug. HU (30‐800 mg/kg) induces a dose‐dependent increase of plasma corticosterone in normal rats after single or repeated treatments that is not observed in hypophysectomized animals. HU also increases plasma levels of epinephrine, although this finding cannot account for the rise in plasma corticosterone; indeed, it is secondary to a strong rise in plasma corticosterone. The stimulation of the hypothalamic‐hypophyseal‐adrenal axis induced by HU is responsible for the drug‐induced adrenocortical activation. This activation appears to be a valuable defence mechanism protecting intact rats against HU lethality, and its failure causes the dramatic HU lethality in pituitary‐ or ad

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00815.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The effect of pertussis toxin (PTX) and the cyclic GMP lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN), isosorbide‐5‐mononitrate (IS‐5‐MN) and sodium nitroprusside (SNP) in bovine mesenteric artery (BMA) was investigated. Pretreatment with PTX (100 ng/ml; 2 hr induced a 100‐fold right shift of the concentration‐effect curve for GTN, while no effect on the relaxatory response elicited by ISDN, IS‐5‐MN or SNP was seen. The relaxatory effect of all the substances tested was markedly reduced by LY83583 (10 μM). The basal cGMP level as well as the GTN induced increase in cGMP were markedly reduced when BMA was exposed to LY83583. The substance also reduced the activation of soluble guanylate cyclase by SNP. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN, IS‐5‐MN and SNP. As far as the GTN induced relaxation is concerned the sensitivity towards PTX indicates the involvement of regulatory component, possibly a G‐protein. However, cyclic GMP seems to play a crucial role in mediating the relaxatory response of all the substances tested since the cGMP‐lowering agent LY83583 markedly inhibited the relaxant response induced by all the vascular rela

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00816.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The distribution of mercury after inhalation of metallic mercury vapour (6‐8 μmol203Hg0/kg b.wt.) was studied in pregnant mice (day 17 of gestation) after pretreatment with selenite (10 μmol Se/kg b.wt. intraperitoneally 1 hr before inhalation), thiram, disulfiram or diethyldithiocarbamate (1 mmol/kg orally 2 hr before inhalation of Hg0). For comparison, the effects of thiram, disulfiram and diethyldithiocarbamate on the distribution of mercury after administration of ionic mercury (7 μmol203HgCl2/kg b.wt. intravenously) were also studied. Selenite pretreatment caused a longer retention of mercury in maternal tissues but decreased the foetal concentrations after203Hg0inhalation, similarly to what has been shown previously after administration of ionic mercury (Hg2+). Pretreatment with the three dithiocarbamates markedly increased the uptake in maternal brain and fat and decreased the foetal concentrations after intravenous injection of203HgCl2. In contrast, no change in foetal uptake and only slight changes in maternal tissue concentration of mercury were observed after treatment with the dithiocarbamates followed by inhalation of203Hg0, compared with203Hg0inhalation alone. The results are in favour of a firmer binding of mercury after Hg0inhalation, when oxidation of Hg0to Hg2+occurs intracellularly, than after Hg2+injection. Further studies, using repeatedly low dose administration of selenium, are needed to draw any conclusions concerning the protective effects of selenium after exposure to metallic mercury va

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00817.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Previous studies from our laboratory have indicated that chlordecone (Kepone®, CD), an organochlorine insecticide, inhibited cardiac sodium pump activity and catecholamine uptake suggesting that CD may interfere with cardiac function. Sarcoplasmic reticulum (SR) calcium pump has an important role in myocardial contraction and relaxation, besides Na+transport. Since CD interferes with cardiac Na+ion translocases, we have studied CD effects on cardiac SR calcium pump activity. Experiments were carried out bothin vitroandin vivo.SR was isolated from heart ventricles of male Sprague‐Dawley rats. Cardiac SR Ca2+‐ATPase,45Ca‐uptake and cAMP as well as calmodulin (CaM) dependent protein phosphorylation were measured. Ca2+‐ATPase was differentiated into low affinity and high affinity forms by measuring the activity using 50 and 0.7 μM free Ca2+respectively. CDin vitroinhibited45Ca‐uptake by SR in a concentration dependent manner with an IC50 value of 7 μM and SR45Ca‐uptake was totally inhibited at 20–30 μM CD. In agreement with this, both high affinity and low affinity Ca2+‐ATPases, which are involved in Ca2+transport across membranes, were also inhibited by CD in a concentration dependent manner with IC50 values of 0.7 and 3.2 μM respectively. Both Ca2+‐ATPase and45Ca‐uptake by cardiac SR were significantly lower in rats treated with CD (25, 50 or 75 mg/kg) when compared to control rats. cAMP as well as CaM significantly elevated the32P‐binding to SR proteinsin vitroto about 70–80%. In the presence of CD, this32P‐binding was reduced, however, not concentration dependent. In agreement within vitrostudies,32P‐bound to proteins was significantly lowered in rats treated with CD. SDS‐polyacrylamide gel electrophoresis of the cardiac SR revealed the presence of at least 30 comassie blue‐stainable bands with mobilities corresponding to molecular weights ranging from 9 to 120 kDa using 15% acrylamide gels. Autoradiographs from samples incubated in the presence of cAMP or CaM indicated32P‐incorporation in 7 bands. Of these, bands corresponding to about 24 kDa and adjacent lower molecular weights decreased in their intensity by CDin vitroas well asin vivo.These results indicate that CD treatment may be reducing SR calcium transport mechanisms by altering phosphorylation of a number of proteins inc

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00818.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The effect of pinacidil, a new antihypertensive vasodilator, was studiedin vitroupon human and porcine Corpus cavernosum andin vivoupon simian Corpus cavernosum.In vitro, pinacidil incubation (10‐5‐10‐3M) was found to induce a concentration‐dependent inhibition of the tissue response to norepinephrine (NE) and high potassium (K+). Likewise a concentration‐related relaxation of the tissue, precontracted with either NE or K+, was seen using pinacidil 10‐5‐10‐3M. Depending on the concentration applied, spontaneous activity as well as tone and amplitude of the contractions were reduced until total relaxation of the tissue was obtained with a pinacidil incubation of 10‐3M.In vivo, 5 mg pinacidil in 0.3 ml solution was injected intracavernosally in 17 monkeys. Sixteen monkeys developed tumescence and 10, rigidity of the penis as well. Only one of 5 showed a decrease in the systemic blood pressure. Pinacidil might be of clinical interest as an agent facilitating erection when give

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00819.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The effect of auranofin (AF), retinoic acid (RA), and three heavy metals reacting with thiol groups (Hg, Cd, Pb) has been compared on a PKC mediated response of intact macrophages (i.e. plasminogen activator (PA) induction) and on purified PKC activity. AF, cadmium chloride, and lead nitrate directly inhibit PKC and hence prevent the induction of PA activity in macrophages stimulated with PMA.In vitro, and in absence of chelators, mercuric chloride is also a potent inhibitor of PKC. However, at the cellular level, the PKC mediated response (PA induction) was not inhibited by non‐cytotoxic concentrations of mercury possibly due to interference of the metal with additional cellular mechanisms such as calcium mobilisation. Direct inhibition of PKC is probably not the mechanism by which retinoids block the activation of macrophage

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00820.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY