摘要:

Studies were carried out to study the effect of endocrine changes on rat cardiac performance, biochemistry, and responses to drugs. Hyperthyroidism increased contractility in rat hearts and enhanced the phosphorylase response to catecholamine. The inotropic response may be due to an increase in cardiac mass while the enzyme changes may be due to several factors. Hypothyroidism decreased force of contraction, enhanced α-adrenergic inotropic and chronotropic responses, and decreased β-adrenergic responses in isolated atrial preparations. An interaction between cyclic AMP and cyclic GMP is suggested as a possible explanation. Diabetes induced by alloxan or streptozotocin produced a decrease in cardiac performance after 42 days which was correlated with a decrease in sarcoplasmic reticulum (SR) Ca2+uptake. Insulin treatment reversed or prevented both SR and functional changes; other treatments were not as successful. Responses to cardiotonic drugs were altered by the diabetic state. The phosphorylase response to isoproterenol was enhanced while the inotropic response was not affected. An initial subsensitivity to carbachol at 30–100 days of diabetes subsequently converted to a supersensitivity to the muscarinic agent. Ouabain responses were decreased in atrial and papillary preparations from diabetic animals. Studies are continuing to elucidate the mechanisms involved in the altered pharmacological responses seen in hearts from diabetic animals.

ISSN:0008-4212    

DOI:10.1139/y85-001

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The effects of substitution of calcium (Ca) by an equimolar concentration of strontium (Sr) on isometric contractions of isolated ventricular muscle from postnatally developing rat heart were studied. The duration of contraction and the time-to-peak tension were increased in all age groups although much less in the adult rats than in the neonates. The contractile force was increased in the muscles of rats between 1 and 14 days of age but was depressed in the older animals. The prominent rest-twitch potentiation of neonatal rat heart in Ca− Tyrode was totally eliminated by Sr, whereas a clear rest-twitch potentiation was induced by this cation in the adult rat heart, in which tissue the potentiation is normally absent in Ca− Tyrode. The maximal twitch potentiation by rest in Ca− Tyrode and the positive inotropic effect of Sr substitution grew from birth up to day 9 and from then gradually declined towards the level of adult rat heart by the end of the 3rd postnatal week. The phase of increasing rest-twitch potentiation coincides fairly well with the known development of sarcoplasmic reticulum and the phase of decline with the appearance of the T system of the sarcolemma. It is suggested that the qualitative changes in the contractile properties of developing rat heart during the 3rd postnatal week are due to the more efficient utilization of intracellular calcium stores, owing to the development of the T system.

ISSN:0008-4212    

DOI:10.1139/y85-002

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The receptor potential in the sensory neuron of the cockroach femoral tactile spine was recently observed by raising the axon into an oil bath and measuring the decrementally conducted receptor current. Although action potential discharge in this receptor adapts rapidly, there was no evidence of adaptation in the receptor potential. In the present work we report that bursts of action potentials in the neuron produce a prolonged after-hyperpolarization and attenuate the receptor potential. Both of these effects could be important in receptor adaptation and we sought to identify their origin. It was impossible to control ionic concentrations in the fluid surrounding the sensory neuron because of an effective glial barrier, but it was possible to infuse the tissues with chemical agents which are known to block ionic membrane processes. Cobalt and cadmium, which inhibit calcium influx, eliminated the effects of action potentials, and ouabain had similar effects. These results suggest that both a calcium-activated potassium conductance and an electrogenic sodium pump are involved in these phenomena. However, it is argued that the former is probably more important.

ISSN:0008-4212    

DOI:10.1139/y85-003

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The effects of three calcium antagonists, verapamil, lanthanum, and 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) were studied on the release of slow-reacting substance of anaphylaxis (SRS-A) from ovalbumin-sensitized chopped guinea pig lung parenchyma in calcium-containing and calcium-free media. The SRS-A levels (mean ± SEM) obtained from tissues incubated in normal and calcium-free Krebs–bicarbonate buffer were 51 ± 8 (N = 19) and 21 ± 4 (N = 14) U/mL, respectively. TMB-8 (0.1–10 μM) a reported intracellular calcium antagonist, reduced antigen-stimulated SRS-A release from lung tissue incubated in calcium-containing, but not calcium-free, medium; A23187-induced SRS-A release from normal guinea pig lung was not significantly altered by TMB-8 at concentrations up to 10 μM. Verapamil and lanthanum consistently reduced SRS-A release only at high concentrations (100 μMand 1 mM, respectively). The quantities of SRS-A released from lung tissue incubated in the presence of verapamil in normal medium were similar to those obtained in calcium-free medium. Tissues incubated in the presence of potassium chloride (60 and 100 mM) did not release significant quantities of SRS-A, and release which did occur was not blocked by verapamil, suggesting that antigen-induced SRS-A release is not dependent on membrane depolarization and that verapamil was not exerting inhibition via blockade of voltage-dependent calcium channels. These data suggest that although intracellular calcium is important for the regulation of SRS-A secretion from guinea pig lung tissue, extracellular calcium is necessary for optimal release of SRS-A.

ISSN:0008-4212    

DOI:10.1139/y85-004

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The purpose of this study was to assess the relationship between muscle fiber type distribution and enzymatic characteristics in sedentary male and female subjects. Muscle biopsy samples from the vastus lateralis muscle of 38 females and 37 males were analyzed to determine the fiber type composition (I, IIa, and IIb), the fiber size, and maximal activities of enzyme markers of energy metabolic pathways. Significant correlations were found (p < 0.05) between percent fiber type I area and hexokinase (r = −0.39), phosphofructokinase (r = −0.39), lactate dehydrogenase (r = −0.41), and oxoglutarate dehydrogenase (r = 0.33) activities, whereas such correlations with total phosphorylase (r = −0.02), malate dehydrogenase (r = 0.12), and 3-hydroxyacyl CoA dehydrogenase (r = 0.12) activities were not significant. The results of the present study also suggest the presence of a significant but low covariation of less than 30% between the fiber type distribution and muscle enzyme activities. They confirm the presence of an important metabolic heterogeneity independent of the muscle fiber type distribution in sedentary male and female subjects. Moreover, these results indicate that sedentary males exhibit a lower mean value of percent fiber type I and higher glycolytic enzyme activities than sedentary females.

ISSN:0008-4212    

DOI:10.1139/y85-005

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Halogenated hydrocarbon insecticides and polychlorinated biphenyl (PCB) mixtures are routinely detected as residues in human adipose tissue, serum, and milk. Based on average values observed in analytical studies, reconstituted halogenated hydrocarbon pesticide mixtures and PCB mixtures were prepared and administered to immature male Wistar rats. The mixtures were administered at dose levels which approximate the concentrations which would be absorbed by an infant suckling for 180 days (low dose, L), and at three higher dose levels (2 × L, 10 × L, and 100 × L). The pesticide mixture contained isomeric hexachlorocyclohexanes, dieldrin, heptachlor epoxide, oxychlordane,trans-nonachlor, hexachlorobenzene, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene; the reconstituted PCB mixture contained 13 of the major congeners which have been identified in human milk samples. Administration of the L dose level of the pesticide (0.95 mg/kg), PCB (0.45 mg/kg), and pesticide plus PCB mixture (0.95 + 0.45 mg/kg, respectively) in corn oil on days 1 and 3 did not significantly alter hepatic drug-metabolizing enzyme activities or elicit any observable pathological damage 6 days after the first exposure. In contrast, administration of the higher dose levels of this mixture elicited a dose-dependent induction of several hepatic drug-metabolizing enzymes. Moreover, despite the short duration of exposure to these chemicals, the rats treated with the higher doses (10 × L and 100 × L) of these mixtures exhibited mild alterations in thyroid architecture, changes in hepatocellular nuclei including variations in chromatin distribution, vesiculation of larger nuclei, and frequent appearance of pyknotic shrunken nuclei. In addition there were changes in hepatocellular cytoplasm organization including vacuolations and mild zonal variations in volume. The results clearly indicate that relatively low doses of the pesticides and pollutant mixtures commonly found in human breast milk can elicit significant biologic and toxic effects in the immature male Wistar rat.

ISSN:0008-4212    

DOI:10.1139/y85-006

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Rb+uptake, intracellular Na+and K+levels, and the tissue–medium distribution of the nonmetabolized glucose analog, 3-O-methyl-D-glucose (3-MG) were measured in rat diaphragms incubated with chiormadinone acetate, 6-chloro-4,6-pregnadien-17-ol-3,20-dione 17-acetate (CMA), in the presence and absence of ouabain. CMA in concentrations of 5 × 10−7 Mor higher significantly depressed86Rb uptake, and promoted an increase in internal Na+and a decrease in internal K+, indicating inhibition of the sodium pump. Sugar transport in resting muscle parallels the changes in internal Na+levels and is an additional indicator of sodium pump activity. Equilibration of 3-MG between tissue and medium was accelerated by CMA, in parallel to the rise in internal Na+level. Effects of CMA on Na+levels and sugar transport, but not on Rb+uptake, were additive to those of various concentrations of ouabain, suggesting interaction with sites not affected by ouabain. These results on diaphragm muscle confirm our previous studies on isolated cardiac muscle preparations showing that CMA, added to the aqueous bathing medium, inhibits the sodium pump in intact muscle tissues.

ISSN:0008-4212    

DOI:10.1139/y85-007

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

In using pharmacologic stimuli, force–velocity (FV) curves are usually obtained by the method of quick release (QR) and redevelopment of shortening at peak tetanic tension; the advantage of the method being that the active state is at maximum. However, the QR may itself reduce the intensity of the active state and result in reduced values of FV constants. We tested this by delineating FV curves in canine tracheal smooth muscle using both conventional afterloaded isotonic contractions (ALI), and redevelopment of shortening after QR methods. For both these studies a supramaximal tetanizing electrical stimulus was used. The analysis of 11 experiments revealed that the latter method resulted in statistically significant reductions of all FV constants except forPo(maximum isometric tetanic tension). The means and standard errors for the sets of constants for the ALI and QR, respectively, are as follows:Vmax(maximum velocity of shortening) = 0.275 lo(optimal muscle length)/s ± 0.024 (SE), and 0.216 lo/s + 0.023;a(hyperbolic constant with units of force) = 294 g/cm2 ± 35 and 236 g/cm2 ± 32;b(hyperbolic constant with units of velocity) = 0.059 lo ± 0.004 and 0.039 lo/s ± 0.005;a/Po = 0.214 ± 0.028 and 0.182 ± 0.026; andPo = 1.362 kg/cm2 ± 0.106 and 1.294 kg/cm2 ± 0.097. These data clearly show that the quick-release method for measuring force–velocity relationships in canine smooth muscle results in significant underestimates of muscle shortening properties.

ISSN:0008-4212    

DOI:10.1139/y85-008

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The influence of experimental diabetes induced by streptozotocin on responses of rat isolated aortae and portal veins to noradrenaline, 5-hydroxytryptamine, and KCl was examined 7, 100, 180, and 360 days after the onset of diabetes. No significant changes in reactivity were seen 7 days after the onset of diabetes. After 100 days aortae from diabetic rats were supersensitive (defined as a significant increase in the pD2value) to noradrenaline. However, 180 days after the onset of diabetes, the sensitivity of diabetic aortae to noradrenaline was not significantly different from control, while the responsiveness (defined as the maximum developed tension ÷ cross-sectional area of aorta) to 5-hydroxytryptamine was reduced. A generalized increase in both the sensitivity and responsiveness of diabetic aortae to all three agonists was observed after 360 days of diabetes. In contrast, no changes in either the sensitivity or the responsiveness of portal veins to noradrenaline, 5-hydroxytryptamine, or KCl could be detected at any time after the onset of diabetes. These results indicate that changes in vascular reactivity can be detected with increasing duration of experimental diabetes. However, these changes do not follow a consistent pattern and are not seen in all parts of the vasculature.

ISSN:0008-4212    

DOI:10.1139/y85-009

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Several amino- and ammonio-substituted derivatives of adenosine were tested as effectors of adenosine receptors in different smooth muscle preparations and mouse neuroblastoma adenylate cyclase. The compounds did not affect adenosine receptors in smooth muscles. N6-[3-(trimethylammonio)propyl]adenosine was a weak stimulator of adenylate cyclase, and 3′-amino-3′-deoxyadenosine and 3′-rnonomethylamino-3′-deoxyadenosine antagonized the stimulation of adenylate cyclase by 2-chloroadenosine.

ISSN:0008-4212    

DOI:10.1139/y85-010

出版商:NRC Research Press    

年代:1985

数据来源: NRC