Noninvasive assessment of local myocardium repolarization changes using high resolution surface ECG mapping

A method using body surface potential maps for assessment of myocardium lesions with changed repolarization is presented and suitable mapping system is introduced. Differences between normal and altered QRST integral maps together with torso volume conductor model were used to determine the equivalent dipole representing the lesion. Performance of the method was studied on simulated data. Changed repolarization was modeled by shortening of myocyte action potentials in regions typical for stenosis of the main coronary arteries. The equivalent dipole estimated the positions of small lesions with a mean error of 9+/-4 mm (17+/-14 mm for larger transmural lesions). The subepicardial or subendocardial character of the lesions was reflected in the dipole orientation. Tests of the method on patients after myocardial infarction that underwent coronary intervention on a single coronary vessel showed that in 7 of 8 successfully treated patients the dipole position matched well with the treated vessel. A small dipole moment in another patient indicated unsuccessful treatment. The method was implemented in a new 128-channel mapping system. Its active electrodes, battery powered measuring unit and optical computer interface help to minimize noise in ECG and guarantee patient's safety. The results suggest that the method and mapping system offer useful tools for noninvasive identification of local repolarization changes in the myocardium.     

Circadian rhythms of feeding and drinking behavior of rats aged from 3 to 21 months

Circadian rhythms and patterns of feeding and drinking behavior of 8 male and 8 female Long-Evans rats were followed from 3 months of age (mo) to 21 mo at 3 month intervals. Meal number, draft number and feeding events/min/meal of female rats were greater than those of male rats of the same age, while intermeal intervals, interdraft intervals and licking events/min/draft of male rats were greater than those of female rats. Sex differences of meal number, intermeal intervals and feeding events/min/meal as a group disappeared by 21 mo. Light/dark differences of meal number of both sexes, intermeal intervals of females and licking events/min/draft of males as a group also disappeared by 21 mo and difference of feeding events/min/meal disappeared by 15 and 18 mo in males and females, respectively. Occurrence of age-related change varied from 6 to 21 mo depending upon the parameter of the behavior and period (light or dark). Meal number and feeding events/min/meal showed the most clear-cut age-related changes and the decline occurred earlier and was more remarkable in males than in females. The age-related decline of patterns and the power spectrum of drinking behavior was less prominent than that of feeding behavior. These results indicate that feeding behavior is more affected by the aging process than is the drinking behavior of rats, and that male rats show more prominent aging changes than females.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic beta-agonist administration affects cardiac function of adult but not old rats, independent of beta-adrenoceptor density

Although beta-adrenoceptor agonists have clinical merit for attenuating the age-related loss of skeletal muscle mass and strength (sarcopenia), potential cardiac-related side effects may limit their clinical application. The aim of this study was to determine whether chronic beta-agonist administration impairs cardiac function in adult or aged rats. Adult (16 mo) and aged (28 mo) Fischer 344 rats were treated with fenoterol (1.4 mg.kg(-1).day(-1) ip) or vehicle for 4 wk. Heart function was assessed in vitro before analyses of cardiac structure and beta-adrenoceptor density. Heart mass increased 17% and 25% in fenoterol-treated adult and aged rats, respectively. The increased heart mass in aged, but not adult, rats was associated with a relative increase in collagen content. Cardiac hypertrophy in adult rats was associated with an increase in left ventricular developed pressure, a marked reduction in cardiac output, and a reduction in coronary flow per unit heart mass. In contrast, negligible differences in ventricular function were observed in fenoterol-treated aged rats. The differential effect on contractile function was not associated with age-related differences in beta-adrenoceptor density but, rather, an age-related increase in downregulation after treatment. Our results show that chronic beta-agonist treatment impairs cardiac function to a greater extent in adult than in aged rats. These results provide important information regarding the potential effects of chronic beta-agonist use on cardiac function and the future development of safe and effective treatments for sarcopenia.     

大鼠缺血性脑损伤引起学习记忆障碍及心率变异性改变

本研究通过建立高脂缺血性脑损伤大鼠模型,进行水迷宫实验和心率变异性（heart rate variability,HRV）的功率谱分析,探讨脑损伤前后大鼠学习记忆的变化及缺血对自主神经的影响。23只成年雄性Wistar大鼠随机分为对照组（n=10）、高脂组（n=6）和高脂缺血组（n=7）。高脂组和高脂缺血组大鼠均饲以高脂饲料制成高血脂大鼠模型。各组大鼠进行水迷宫实验后,高脂缺血组用双侧颈总动脉结扎（2-VO）法制作缺血再灌注模型,同时记录心电图。7d后各组大鼠再次进行水迷宫实验和记录心电图,对HRV序列进行基于快速傅立叶转换（fast Fourier transformation,FFT）的功率谱分析。结果：（1）第一次水迷宫测试,3组大鼠空间探索实验和定位航行实验结果无统计学差异;第二次水迷宫实验,高脂缺血组与其它两组相比,空间探索实验中平台所在象限的记忆频度明显下降（P〈0．01）,定位航行实验中平台所在象限的记忆频度显著下降（P〈0．01）,10圆环记忆得分显著下降（P〈0．001）,但高脂组与对照组相比无明显差异。（2）高脂缺血组缺血后心率持续下降;缺血时HRV中频段功率（0．2加．6Hz）呈现明显下降的趋势,高频段功率（0．6-2．5Hz）缓慢下降,中频／高频功率比值明显下降（P〈0．05）。（3）缺血7d后高脂缺血组与高脂组相比,心率明显加快,HRV的中频段功率无显著变化,高频段功率明显下降,中频／高频功率比值显著增高（P〈0．05）。结果表明,缺血过程中高脂缺血组大鼠的自主神经活动降低,交感神经活动相对于迷走神经活动减弱。缺血7d后,由于海马区神经元对缺血敏感易受损,造成高脂缺血组大鼠学习记忆障碍,同时引发迷走神经活动下降,大鼠交感．迷走神经系统平衡失调。     

Theoretical analysis of the magnetocardiographic pattern for reentry wave propagation in a three-dimensional human heart model

We present a computational study of reentry wave propagation using electrophysiological models of human cardiac cells and the associated magnetic field map of a human heart. We examined the details of magnetic field variation and related physiological parameters for reentry waves in two-dimensional (2-D) human atrial tissue and a three-dimensional (3-D) human ventricle model. A 3-D mesh system representing the human ventricle was reconstructed from the surface geometry of a human heart. We used existing human cardiac cell models to simulate action potential (AP) propagation in atrial tissue and 3-D ventricular geometry, and a finite element method and the Galerkin approximation to discretize the 3-D domain spatially. The reentry wave was generated using an S1-S2 protocol. The calculations of the magnetic field pattern assumed a horizontally layered conductor for reentry wave propagation in the 3-D ventricle. We also compared the AP and magnetocardiograph (MCG) magnitudes during reentry wave propagation to those during normal wave propagation. The temporal changes in the reentry wave motion and magnetic field map patterns were also analyzed using two well-known MCG parameters: the current dipole direction and strength. The current vector in a reentry wave forms a rotating spiral. We delineated the magnetic field using the changes in the vector angle during a reentry wave, demonstrating that the MCG pattern can be helpful for theoretical analysis of reentry waves.     

Intracardiac expression of neutral endopeptidase

Neutral endopeptidase (NEP), a proteolytic enzyme, is known to degrade several peptides which control cardiovascular homeostasis. This is a preliminary study of the pattern of the intracardiac regional expression of the NEP gene in the normal heart, and the age-related changes in this expression in the cardiac regions. The relative abundance of NEP mRNA was determined by RT-PCR in the right atrium (RA), right ventricle (RV), left atrium (LA), left ventricle (LV) and interventricular septum (IVS) in 2-month-old (young) and 12-month-old (advanced-age adult) Wistar Kyoto (WKY) rats. The NEP gene was expressed in all 5 cardiac regions in both age groups. In young rats, the NEP expression level was lowest in the RA; this level was significantly lower than in the septum (p > 0.05). In the advanced-age adult rats, the level was lowest in the LA; this level also was significantly lower than in the septum (p > 0.05). The level in the RA in advanced-age rats was higher than that in the young rats (p < 0.01), but the levels in other regions were not significantly different between the young rats and advanced-age adult rats. Our study showed that the NEP gene was expressed in all cardiac regions of both young rats and advanced-age adult rats. However, the regional distribution of the gene was different in each age group. The region-specific expression of the NEP gene and the age-related regional changes in the expression may be due to the structural and functional characteristics of the various regions.     

Diurnal rhythmicity of norepinephrine activity associated with the estradiol-stimulated luteinizing hormone surge: effect of age and long-term ovariectomy on hemispheric asymmetry

The age-related decline in female reproductive capacity in rats is accompanied by an inability to respond positively to estradiol (E2) treatment. This age-related change is associated with a loss in diurnal rhythmicity of norepinephrine (NE) activity in brain areas important in the control of LH. Decreased exposure to ovarian secretions during adulthood delays certain aspects of neuroendocrine aging. We tested the hypothesis that long-term ovariectomy (OVX) would delay the age-related loss of diurnal rhythmicity in NE activity in microdissected hypothalamic nuclei. Intrigued by reports of lateralization of hypothalamic function, we also assayed NE activity in the left and right sides of the hypothalamus separately. Young (2-3 mo) and middle-aged (11-12 mo) rats that exhibited regular estrous cycles were OVX. One week later (Day 0) these short-term OVX animals (Y-ST, MA-ST) plus a group of middle-aged (11-12 mo) rats that were OVX at 3 mo (MA-LT) were treated with E2. On Day 4, the rate constant of NE activity in microdissected hypothalamic nuclei was determined at 0900 h and 1500 h using the alpha-methyl-para-tyrosine method. Rate constants were compared by t-test to determine diurnal rhythmicity. Y-ST rats exhibited a diurnal rhythm in NE activity in the median eminence, which was absent in MA-ST rats. Long-term OVX spared animals this "age-related" loss in rhythmicity since MA-LT rats demonstrated a significant increase in NE activity from morning to afternoon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-related changes in renal and hepatic cellular mechanisms associated with variations in rat serum thyroid hormone levels

Aging is associated with changes in thyroid gland physiology. Age-related changes in the contribution of peripheral tissues to thyroid hormone serum levels have yet to be systematically assessed. Here, we investigated age-related alterations in the contributions of the liver and kidney to thyroid hormone homeostasis using 6-, 12-, and 24-mo-old male Wistar rats. A significant and progressive decline in plasma thyroxine occurred with age, but triiodothyronine (T(3)) was decreased only at 24 mo. This was associated with an unchanged protein level of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in the kidney and with a decreased MCT8 level in the liver at 24 mo. Hepatic type I deiodinase (D1) protein level and activity declined progressively with age. Renal D1 levels were decreased at both 12 and 24 mo but D1 activity was decreased only at 24 mo. In the liver, no changes occurred in thyroid hormone receptor (TR) TRalpha(1), whereas a progressive increase in TRbeta(1) occurred at both mRNA and total protein levels. In the kidney, both TRalpha(1) and TRbeta(1) mRNA and total protein levels were unchanged between 6 and 12 mo but increased at 24 mo. Interestingly, nuclear TRbeta1 levels were decreased in both liver and kidney at 12 and 24 mo, whereas nuclear TRalpha(1) levels were unchanged. Collectively, our data show differential age-related changes among hepatic and renal MCT8 and D1 and TR expressions, and they suggest that renal D1 activity is maintained with age to compensate for the decrease in hepatic T(3) production.     

Insight into the role of DL-α-lipoic acid against cyclophosphamide induced alterations in calcium sensitivity of cardiac myofilaments

Cyclophosphamide (CP), a potent antitumor drug, is known to cause severe cardiotoxicity. The present study is aimed at evaluating the role of DL-α-Lipoic acid (LA) on the calcium responsiveness of cardiac myofilaments isolated from CP treated rats. Adult male Wistar rats were divided into four treatment groups. Two groups received single intraperitoneal injection of CP (200 mg/kg b.wt.) to induce cardiotoxicity, one of these groups received LA treatment (25 mg/kg b.wt. for 10 days). A vehicle treated control group and a LA drug control were also included. Cardiotoxicity was evident from increased levels of cardiac Troponin I in serum of CP treated rats. The pCa-actomyosin ATPase relationship of myofilaments demonstrated a rightward shift indicating diminished responsiveness in CP treated rats. The hill coefficient was reduced and the myofibrillar myosin Ca²⁺-ATPase and K⁺-(EDTA) activities were also significantly (P < 0.05) reduced. Ultrastuctural observations were also in agreement with the above abnormal changes, wherein loss of myofilaments occurred. LA effectively normalized these abnormalities and restored the cardiac function in CP administered rats.     

Vagus nerve stimulation suppresses generalized seizure activity and seizure-triggered postictal cardiac rhythm changes in rats

In the present study, we investigated the effects of vagus nerve stimulation (VNS), a proposed treatment for patients with intractable epilepsy, on cardiac rhythm following seizures induced by pentylenetetrazole (PTZ) in Wistar rats. After a baseline recording of electroencephalogram (EEG), electrocardiogram (ECG) and blood pressure (BP), rats in the first group received a single convulsive dose of PTZ (70 mg/kg) (Group 1). In the other two groups, the Wistar rats were implanted with a cuff electrode on the left cervical vagus nerve. One day after surgery, rats in the second group were treated with VNS (Group 2), whereas rats in the third group were connected to the stimulator but did not receive VNS (Group 3). Ten minutes after VNS onset, 70 mg/kg dose of PTZ was injected. EEG, ECG and BP were continuously recorded during post-injection period. Seizure severity was scored behaviorally. Then, baseline, ictal and postictal periods were analyzed for cardiac rhythms, seizure severity and blood pressure variability. PTZ treatment induced tonic-clonic seizure activity in all animals of Group 1 and Group 3. In these groups a marked increase of mean arterial blood pressure (MABP) but a significant decrease in heart rate and PP interval fluctuations was observed at postictal period. However, in the VNS-treated group the seizure scores and cardiac parameter returned to the baseline level. Present results emphasize that VNS effectively reduces seizure severity and suppress the seizure-induced cardiac rhythm changes.     

Electron microscopical findings with special reference to cancer in rats caused by inhalation of nickel oxide

A special exposure system was used for the inhalation of nickel oxide (NiO) aerosol by Wistar male rats. The median aerodynamic diameter and the geometric standard deviation were 1.2 μm and 2.2, respectively. A histopathological study of the rats was performed immediately, and at intervals of 12 and 20 mo after a 1-mo expsoure to NiO. Electron microscopy showed that localization of NiO particles was restricted to the lungs and that each particle had been engulfed by the alveolar macrophages. Type II pneumocytes and nonciliated bronchiolar epithelial cells (Clara cells), as well as numerous tubular myelin (surfactant) in the alveoli were prominent. In rats dissected after 12 mo, clusters of NiO particles were still present within the terminal bronchioli, alveolar walls, and lysosomes of the alveolar macrophages. Pools of tubular myelin were observed in the peribron-chial lymphatics. The Clara cells, which project into the lumen of bronchioli, showed active secretion and were filled with smooth en-doplasmic reticulum (SER) in the apical cytoplasm. In the experimental group sacrificed after 20 mo, one rat had papillary adenocarcinoma and two rats showed adenomatosis in the peripheral portion of the lung, but none in the upper respiratory tract.     

The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats

In this study, the aphrodisiac activities of Crocus sativus stigma aqueous extract and its constituents, safranal and crocin, were evaluated in male rats. The aqueous extract (80, 160 and 320 mg/kg body wt.), crocin (100, 200 and 400 mg/kg body wt.), safranal (0.1, 0.2 and 0.4 ml/kg), sildenafil (60 mg/kg body wt., as a positive control) and saline were administered intraperitoneally to male rats. Mounting frequency (MF), intromission frequency (IF), erection frequency (EF), mount latency (ML), intromission latency (IL) and ejaculation latency (EL) were the factors evaluated during the sexual behavior study. Crocin, at all doses, and the extract, especially at doses 160 and 320 mg/kg body wt., increased MF, IF and EF behaviors and reduced EL, IL and ML parameters. Safranal did not show aphrodisiac effects. The present study reveals an aphrodisiac activity of saffron aqueous extract and its constituent crocin.     

Noninvasive three-dimensional electrocardiographic imaging of ventricular activation sequence

Imaging the myocardial activation sequence is critical for improved diagnosis and treatment of life-threatening cardiac arrhythmias. It is desirable to reveal the underlying cardiac electrical activity throughout the three-dimensional (3-D) myocardium (rather than just the endocardial or epicardial surface) from noninvasive body surface potential measurements. A new 3-D electrocardiographic imaging technique (3-DEIT) based on the boundary element method (BEM) and multiobjective nonlinear optimization has been applied to reconstruct the cardiac activation sequences from body surface potential maps. Ultrafast computerized tomography scanning was performed for subsequent construction of the torso and heart models. Experimental studies were then conducted, during left and right ventricular pacing, in which noninvasive assessment of ventricular activation sequence by means of 3-DEIT was performed simultaneously with 3-D intracardiac mapping (up to 200 intramural sites) using specially designed plunge-needle electrodes in closed-chest rabbits. Estimated activation sequences from 3-DEIT were in good agreement with those constructed from simultaneously recorded intracardiac electrograms in the same animals. Averaged over 100 paced beats (from a total of 10 pacing sites), total activation times were comparable (53.3 +/- 8.1 vs. 49.8 +/- 5.2 ms), the localization error of site of initiation of activation was 5.73 +/- 1.77 mm, and the relative error between the estimated and measured activation sequences was 0.32 +/- 0.06. The present experimental results demonstrate that the 3-D paced ventricular activation sequence can be reconstructed by using noninvasive multisite body surface electrocardiographic measurements and imaging of heart-torso geometry. This new 3-D electrocardiographic imaging modality has the potential to guide catheter-based ablative interventions for the treatment of life-threatening cardiac arrhythmias.     

Aging and Lateralization of the Rat Brain on a Biochemical Level

It has been suggested that the lateralization of the human brain underlies hemispheric specialization and that it can be observed also on a biochemical level. Biochemical laterality appears to be a basis of volumetric or functional asymmetry but direct relationships among them are still unclear. Moreover, age-related differences between the right and left hemispheres are not well documented in various rat strains. In the current study, biochemical markers sensitive to Alzheimer disease (activities of high-affinity choline uptake and of nitric oxide synthases, expression of 17β-hydroxysteroid dehydrogenase type 10) were estimated in both hemispheres of young and old male Wistar/Long Evans rats. Our experiments indicate (1) differences in some biochemical markers between young Wistar and Long Evans rats (the activities of endothelial nitric oxide synthase are higher in Long Evans and those of citrate synthase in Wistar rats), (2) more similar brain asymmetry of healthy human/young Wistar brains when compared to those of young Long Evans, (3) the decrease in asymmetry of the physiologically left/right lateralized biomarker during aging (the activity of the high-affinity choline uptake decreases more markedly in the left side of old Wistar rats) in accordance with the HAROLD model, (4) the age-related shift to reversed left/right asymmetry of the physiologically right/left lateralized biomarker (the activity of inducible nitric oxide synthase increases especially in the left side of old Long Evans rats), and finally (5) age-related differences in physiologically unlateralized biomarkers between Wistar and Long Evans rats (changes in the activities of neural/endothelial nitric oxide synthases or in expression of 17β-hydroxysteroid dehydrogenase type 10 are more asymmetrical in old Wistar when compared to rather bilateral alterations of old Long Evans animals). It seems that the physiological lateralization of the human or rat brains on a biochemical level and their age-related alterations are dependent on biomarker type/function. By our opinion, it is difficult, perhaps impossible, to make one simple universal model, at least on a biochemical level. Since lateral analyses are of sufficient sensitivity to reveal subtle links, we recommend using Wistar rather than Long Evans rats in modeling of diseases accompanied by alterations in brain asymmetry.     

Myocardial hypertrophy of normotensive Wistar-Kyoto rats

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 +/- 0.03 mg/g, n = 41) was intermediate between SHR (2.82 +/- 0.04 mg/g, n = 47) and Wistar rats (1.98 +/- 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.     

Myocardial remodeling and arrhythmogenesis in moderate cardiac hypertrophy in rats

In 47 male adult Wistar rats with 4-wk aortic coarctation (AC) and 39 age-matched sham-operated rats (SO) chronically instrumented for telemetry electrocardiogram recording, we investigated the mechanisms of arrhythmogenesis in moderate cardiac hypertrophy, with an approach from "in vivo" toward the cellular level, analyzing 1) stress-induced cardiac arrhythmias in all rats and 2) myocardial fibrosis in 35 animals and action potential duration and density of hyperpolarization-activated current in 19 others at the ventricular level. Aortic banding increased arterial blood pressure, cardiac weight, and ventricular myocyte volume by 11, 25, and 14%, respectively (P < 0.001-0.05). Ventricular arrhythmias occurred at similar rates in AC and SO rats throughout the stress procedure. Action potential duration and hyperpolarization-activated current were about twice as great and myocardial fibrosis about four times greater in AC animals (P < 0.005-0.05). Electrocardiogram data also revealed more supraventricular arrhythmias in AC rats during the baseline period and after stress and fewer atrioventricular block episodes after stress (P < 0.05). Thus stress-induced supraventricular and atrioventricular nodal, but not ventricular, arrhythmias were affected in moderate cardiac hypertrophy when ventricular morphofunctional alterations were evident.     

The Sensitivity of Cognitive Processes to the Inhomogeneity of Natural Magnetic Fields

Three experiments were carried out to study the influence of inhomogeneity of natural magnetic field (MF) on animal cognition. Wistar rats (n = 90) were placed in a complicated problem environment, in which they were to form food-operant behavior under conditions of natural MF (Cond. 1) and MFs produced by iron objects (Cond. 2) or by magnets (Cond. 3). Unlike the control group (Cond. 1), all rats in Cond. 2 and 3 were unable to form operant behavior. Weak MF caused both locomotor and emotional depression, and there was no exploratory activity shown during 6 sessions. Brief external stimulation removed locomotor depression, and animals formed operant behavior similar to latent learning (Cond. 2) or “insight” (Cond. 3). Performance efficiency was lower while the level of stress manifestation was higher in Cond. 2 and 3 than in the control at the stage of stabilization. It has been proposed that MF reduces the activity of brain motivation centers and prevents the development of complicated forms of cognitive activity.     

Diaphragm muscle and its feed artery after chronic respiratory airway obstruction in rats

A chronic respiratory load was produced in Wistar rats by tracheal binding to produce a twofold increase of pleural pressure oscillation amplitude during respiration. Eight weeks after the surgery, a higher proportion of type-I muscle fibers (MFI) in the costal diaphragm along with a greater MFI cross-section area and a higher succinate dehydrogenase activity in MFII in the lumbar diaphragm were observed. During recording the mechanical activity of ring preparations of diaphragm arteries under isometric conditions, an increase in endothelium-dependent relaxation was found, whereas endothelium-independent relaxation and arterial reactivity to noradrenaline did not change. Tracheal binding did not produce any changes of MF in the gastrocnemius muscle, but endothelium-dependent relaxation of gastrocnemius feed arteries was reduced. We conclude that chronic respiratory load affects the endothelial function in diaphragm arteries in a manner favorable for blood flow control in the diaphragm. Functional alterations in gastrocnemius arteries may be associated with the reduced locomotor activity of operated rats.     

Changes in the diaphragm muscle and its feed artery after chronic respiratory airway obstruction in rats

A chronic respiratory load was produced in Wistar rats by tracheal binding to produce a twofold increase of pleural pressure oscillation amplitude during respiration. Eight weeks after the surgery, a higher proportion of type-I muscle fibers (MFI) in the costal diaphragm along with a greater MFI cross-section area and a higher succinate dehydrogenase activity in MFII in the crural diaphragm were observed. During recording the mechanical activity of ring preparations of diaphragm arteries under isometric conditions, an increase in endothelium-dependent relaxation was found, whereas endothelium-independent relaxation and arterial reactivity to noradrenaline did not change. Tracheal binding did not produce any changes of MF in the gastrocnemius muscle, but endothelium-dependent relaxation of gastrocnemius feed arteries was reduced. We conclude that chronic respiratory load affects the endothelial function in diaphragm arteries in a manner favorable for blood flow control in the diaphragm. Functional alterations in gastrocnemius arteries may be associated with the reduced locomotor activity of operated rats.