摘要:

On the basis of the morphofunctional evidence obtained in old brains of humans and mammals the present hypothesis has been introduced. This hypothesis states that neuronal plasticity can be used either to compensate for neuronal degeneration or to store new information. Thus, in pathological ageing the marked rate of degeneration has fully exhausted the already reduced plasticity capability of neural networks. In this way marked impairments of memory trace formation take place in pathological ageing conditions such as Alzheimer's disease. The essence of this hypothesis is that a competition for the available plasticity exists between the compensatory responses to ageing‐induced degeneration and the processes necessary for memory trace formation. We have called this hypothesis the ‘Red Queen Theory’, an analogy borrowed from Lewis Carroll's bookThrough the Looking Glass. Thus, in ageing, processes responsible for plasticity must be forced to run at the highest possible rate to maintain the morphofunctional substrate of the existing networks as well as to allow the formation of new memory t

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09370.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Heart rates (HR) of awake unrestrained animals, isometric contraction duration and force‐frequency relationship of ventricular tissue were determined in adult and postnatally developing rats. Resting HR was lowest in newborns (256 beats min‐1), reached maximum at the age of 2.5 weeks (506 beats min‐1) and then declined to the level of adult rats (381 beats min‐1). Duration of isometric contraction correlated negatively with HR. Time to peak tension (TPT) was 185 ms in newborns but fell rapidly during the first days of post‐natal life. Minimum was attained at the age of 2.5 weeks (TPT = 98 ms), followed by a slight prolongation towards adulthood. Recirculating fraction of activator Ca2+increased parallel with HR, being 6% in newborns, 33% in 11‐day‐old pre‐weanlings, and 87% in adult rats. Similar developmental pattern of the parameters suggests that a post‐natal increase in HR and a shortening of contraction duration are closely associated with a shift from extracellular to intracellular source of activator Ca2+. Force–frequency curves were similar at different developmental stages and consisted of three phases; a negative staircase between 0.05 and 1.0 Hz, a positive staircase between 1.0 and 4.0 Hz, and a secondary decline above 4.0 Hz. In adult rats the positive force staircase was weak or absent. Furthermore, our results show that negative staircase is not only a property of adult rat heart but is present, and even more pronounced, in preweanling and weanling rat heart. Therefore negative staircase is not solely explained by quantitative changes in the contribution of sarcoplasmic reticulum (SR) to contractile activation, but rather by the mechanisms which regulate loading and/or release of sarcopla

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09371.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Several inotropic interventions were studied in thin papillary muscles under dynamic conditions. The effects on mechanical restitution and postextrasystolic potentiation were analysed. The decay of postextrasystolic potentiation was taken as a measure of recirculation fraction of activator calcium. The mechanical restitution curve had a plateau phase on its rising phase which was abolished in low extracellular sodium hut pronounced in increased extracellular calcium. The recirculation fraction (RF) in control was 0.35±0.03; lowering the extracellular sodium by 200, increased the RF to 0.46±0.04 (n= 10). A reduction of sodium by 40%, increased the RF to 0.57±0.04, whereas increasing extracellular calcium to 4 mm gave an RF of 0.48±0.05 (n= 10 in all cases). There was no significant effect on RF of changing basic stimulation frequency or muscle preparation length. These findings support RF as a good index of myocardial contractility. Furthermore, at muscle diameters above 0.65 mm the RF was found to he reduced, suggesting this diameter as critical for muscle function. Also, postextrasystolic potentiation in relation to preceding steady state contraction was markedly increased at these diameters.In conclusion, this study shows that RF is independent of stimulation frequency and muscle length, and that it is increased when calcium extrusion by the sodium/calcium exchange is reduced. Furthermore, RF is critically dependent upon the diameter of the preparation and mechanical restitution is changed by altered extracellular sodium concentrat

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09372.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Interactions between angiotensin II and adrenoceptor‐mediated effects on peripheral sympathetic neurotransmission were investigated in constant flow blood‐perfused canine gracilis musclein situ, without and with pretreatment by non‐competitive α‐ adrenoceptor blockade.Angiotensin converting enzyme (ACE)‐inhibition by benazeprilat increased nerve stimulation (2 Hz, 4 min)‐evoked noradrenaline (NA) overflow (+21 ± 5 yo) with α‐ adrenoceptors intact, but reduced NA overflow (– 18 ± 6%) when α‐adrenoceptors were blocked. Vasoconstrictor responses were slightly reduced by benazeprilat. Subsequent infusion of angiotensin II (Ang 11, 20 and 500 ng kg‐1min‐1i.v., raising arterial concentrations from 0.6 ± 0.2 PM to 1390 ± 240 and 25 110 ± 3980 PM, respectively) failed to increase NA overflow or to enhance stimulation‐evoked vasoconstriction. Adrenaline (0.4 nmol kg‐1min‐1i.v.) did not change evoked NA overflow before or after benazeprilat, either with or without α‐adrenoceptor blockade, despite high concentrations (± 10 nM) in arterial plasma. Following benazeprilat, propranolol reduced NA overflow (–24 ± 3 yo) only if the α‐adrenoceptors were blocked.In conclusion, benazeprilat reduced evoked NA overflow in the presence of α‐ adrenoceptor blockade to a similar degree as previously shown in the presence of neuronal uptake inhibition in this model. However, contrasting to our previous findings, benazeprilat enhanced NA overflow and reduced the post‐junctional response to nerve stimulation in the absence of α‐adrenoceptor blockade. This could be related to bradykinin accumulation during ACE‐inhibition, in addition to the reduction of Ang II generation. Our data are not compatible with facilitation of NA release by circulating Ang II even at pharmacological dose levels. Although activation of prejunctional β‐adrenoceptors may facilitate evoked NA overflow in this model, circulating adrenaline is ineffective under physiological conditions even after α‐adrenoceptor blockade. Also, β‐adrenoceptor‐mediated prejunctional effe

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09373.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Subjects cycled at a work load calculated to elicit 75% of maximal oxygen uptake on two occasions: the first to fatigue (34.5 ± 5.3 min; mean ± SE), and the second at the same workload and for the same duration as the first. Biopsies were obtained from the quadriceps femoris muscle before and immediately after exercise, and 5 min post‐exercise. Before the first experiment, muscle glycogen was lowered by a combination of exercise and diet, and before the second, experiment muscle glycogen was elevated. In the low glycogen condition (LG), muscle glycogen decreased from 169 ± 15 mmol glucosyl units kg‐1dry wt at to rest to 13 ± 6 after exercise. In the high glycogen condition (HG) glycogen decreased from 706 ± 52 at rest to 405 ± 68 after exercise. Glycogen synthase fractional activity (GSF) was always higher during the LG treatment. During exercise in the HG condition, those subjects who cycled for35 min (n= 4) had values which were similar to or higher than at rest. Thus the change in GSF in muscle during HG was positively related to the exercise duration (r= 0.94; y = 254–17x + 0.3x2;P<0.001) and negatively related to the glycogen content at the end of exercise (r=–0.82;y= 516–2x + 0.001x2;P<0.05). During LG exercise GSF remained constant. GSF increased markedly after 5 min post‐exercise in both HG and LG conditions. cAMP dependent protein kinase activity increased similarly during both LG and HG exercise and reverted to the preexercise values 5 min post‐exercise. It is concluded that muscle contraction decreases GSF, but low glycogen levels can attenuate or abolish the decrease in GSF. The rapid increase of GSF during recovery from exercise does not require glycogen depletion

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09374.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Experiments were performed on isolated rat soleus (slow‐twitch) and extensor digitorum longus (EDL) (fast‐twitch) muscle of 4‐week‐old rats. In soleus muscle, electrical simulation at 2 Hz for 5 min increased the ouabain‐suppressible86Rb+uptake by 138%, without significant changes in intracellular Na+content or Na+/K+ratio. In EDL muscle, the ouabain‐suppressible86Rb+uptake was stimulated by only 58%, whereas intracellular Na+content and Na+/K+ratio were increased by around 70%. Na+‐loading of the muscles by exposure to K+‐free or K+‐Ca2‐Mg2+‐free buffer stimulated the ouabain‐suppressible86Rb+uptake in the two muscles to roughly the same extent, but in EDL muscle this was associated with a more than twofold larger increase in Na+/K+ratio. When the Na+influx was increased by exposure to veratridine similar results were obtained. Graded variation in intracellular Na+content was achieved by exposure to monensin. In soleus muscle, a 25% increase in intracellular Na+/K+ratio resulted in a doubling of the ouabain‐suppressible86Rb+uptake, whereas a doubling of the Na+–K+transport rate in EDL muscle required a 140% increase in Na+/K+ratio. The results indicate that in soleus muscle the Na+/K+pump is much more sensitive to changes in intracellular Na+content than in EDL muscle. This might explain the larger activation of the Na+–K+pump in slow‐twitch muscle during electrical stimulation and might be of significance for the activation of t

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09375.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The present work has examined the distribution of the two isoforms of monoamine oxidase (MAO), type MAO‐A and MAO‐B, in the cortex and medulla of the human and rat kidney. Homogenates of renal cortex and renal medulla were prepared in 67 mmoles 1‐1phosphate buffer (pH = 7.2) and MAO activity was determined with [3H]5‐hydroxytryptamine ([3H]5HT) and [14C]β‐phenylethylamine ([14C]β‐PEA) as preferential substrates of type A and type B MAO, respectively. KmandVmaxvalues for the two substrates were also calculated. Both MAO‐A and MAO‐B are present in the cortex and the medulla of the human and rat kidneys. In the human kidney, MAO‐A activity was found to be similar in the cortex (Vmax= 142.70±45.05 nmoles mg‐1protein h‐1) and medulla (Vmax= 133.91±35.51 nmoles mg‐1protein h‐1); MAO‐B activity was found to be higher in the cortex (Vmax= 166.19±19.75 nmoles mg1protein h‐1) than in the medulla (Vmax= 92.91±13.22 nmoles mg‐1protein h‐1). In the rat kidney, MAO‐A was also found to be similar in the cortex (Vmax= 62.35±1.74 nmoles mg‐1protein h‐1) and the medulla (Vmax= 59.42±0.97 nmoles mg‐1protein h‐1) and higher than the activity of MAO‐B in the two renal areas (cortex,Vmax= 31.06±1.09 nmoles mg‐1protein h‐1; medulla,Vmax= 14.93±0.97 nmoles mg‐1protein h‐1). No statistically significant differences were found between the Kmvalues towards [3H]5HT and [14C]β‐PEA in the cortex and the medulla of the human and rat kidneys. The results show that in both renal areas, activity of the enzyme is higher in the human kidney than in the rat kidney. Furthermore, in the human kidney, in contrast

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09376.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Experiments were undertaken in two groups of barbiturate anaesthetized dogs to examine whether atrial natriuretic factor (ANF) exerts an effect on renal release of prostaglandin E2(PGE2). In the first group, intravenous infusion of ANF (50 ng min‐1kg‐1body wt) reduced basal PGE2release from 4.4 ± 0.8 pmol min‐1to 1.8 ± 0.7 pmol min‐1. In the second group, intrarenal infusion of an α‐adrenoceptor agonist, phenylephrine (2.5–6.75 μg min‐1), raised PGE2release from 2.7 ± 0.5 pmol min‐1to 7.5 ± 1.3 pmol min‐1. During continuous α1‐adrenergic stimulation, intravenous infusion of ANF (100 ng min‐1kg‐1body wt) reduced PGE2release to 3.5 ± 1.0 pmol min‐1. These results demonstrate that ANF reduces basal and α1‐adr

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09377.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Plasma oestradiol‐17β was measured by RIA, in female,Rana esculenta, submitted to hypophysectomy, gonadectomy, or both, and treated with mammalian gonadotropinreleasing hormone (mGnRH), homologous pituitary homogenate, or both, during the post‐reproductive period. In addition, the oestradiol‐17β release was measured inin vitroincubations of ovaries or interrenals treated with mGnRH, pituitary, or both, during the same period.In vivoandin vitromGnRH and/or pituitary directly stimulated the production of oestradiol‐17β by the interrenal, but not by ovary, although the stimulatory effects of the pituitary are minor and delayed with respect to those of mGnRH.These results seem to indicate that mGnRH and pituitary, with probably different mechanisms, stimulate the interrenal to produce high levels of oestradiol which is involved in the post‐reproductive re

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09378.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

This study was designed to examine the actions of ANP in acute, ANGII‐mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n= 6). ANP (2 μrg min‐1), ANGII (0.5 μg min‐1), or ANGII + ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5–10 mmHg both in pregnancy and in non‐pregnancy. When ANGII + ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 μmol min‐1in non‐pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII‐induced natriuresis to near 3000 μmol min‐1in both non‐pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood‐pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non‐pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1992.tb09379.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY