Alterations in atrial and plasma atrial natriuretic factor (ANF) content during development of hypoxia-induced pulmonary hypertension in the rat

Distension of the atrial wall has been proposed as a signal for the increased release of atrial natriuretic factor (ANF) from atrial myocytes in response to perceived volume overload. To determine whether pressure changes resulting from hypertension in the pulmonary circulation may stimulate release of ANF, rats were exposed to chronic hypobaric hypoxia for 3 or 21 days and the ANF concentration in the atria and plasma were determined by specific radioimmunoassay. Exposure to chronic hypoxia resulted in significant increases in hematocrit at both 3 (p less than 0.025) and 21 days (p less than 0.005) and in the development of right ventricular hypertrophy (RVH) expressed as the ratio of the weight of the right ventricle to the weight of the left ventricle and septum (RV/LV+S) at both 3 (RV/LV+S = 0.278 +/- 0.005) and 21 days (RV/LV+S = 0.536 +/- 0.021). After 21 days, left atrial (LA) ANF content was significantly increased in hypoxic rats compared to controls (508 +/- 70 ng/mg tissue vs 302 +/- 37 ng/mg), while right atrial (RA) ANF content was significantly reduced (440 +/- 45 vs 601 +/- 58 ng/mg). At this time, plasma ANF concentration was significantly elevated compared to controls (238 +/- 107 pg/ml vs 101 +/- 10 pg/ml). These results suggest that the development of pulmonary hypertension following chronic hypobaric exposure induces altered atrial ANF content and increased plasma ANF concentration as a result of altered distension of the atrial wall.     

Arsenic contamination of groundwater and prevalence of arsenical dermatosis in the Hetao plain area,Inner Mongolia,China

The present study determined cardiac chamber-specific alterations of the expression of the atrial and brain natriuretic peptide (ANP and BNP) genes with a small increase in age beyond adulthood and with systemic hypertension of intermediate duration. The expression distributions of these genes was determined using in situ hybridization in the right and left atria (RA and LA), and the right and left ventricles (RV and LV) in Wistar Kyoto rats (WKY) and age-matched Spontaneously Hypertensive rats (SHR) at ages 6 months (adult) and 8 months (advanced-age beyond adulthood).In all rat groups, both genes were expressed (ANP > BNP) in the LA and LV, and were not expressed in the RA and RV. The genes were expressed in the LA in all rat groups; the ANP, but not the BNP, expression increased with advancing age and with superimposed hypertension. They were expressed in the LV of the advanced-age WKY, adult and advanced-age SHR, but not in the adult WKY. The ANP mRNA labeling in the LA was diffuse and interspersed with dense accumulations, whereas BNP labeling was diffuse. The labeling of both genes in the form of sparse clusters was seen in the LV of the advanced-age SHR. Our study showed that ANP and BNP expression in left heart chambers increased with a small increase in age, with hypertension of intermediate duration, and with modest left ventricular hypertrophy. The chamber-specific expression distribution could be due to special groups of cardiac cells, or to local chamber-specific factors.     

Nitric oxide modulates intensity of non-quantal acetylcholine release in myocardium of the right atrium of rat

The main parasympathetic neurotransmitter acetylcholine (ACh) is released in the myocardium from the intramural postganglionic parasympathetic nerve endings. The mechanism of non-quantal ACh release has been recently demonstrated in these neurons. Non-quantal ACh release does not depend on exocytosis of ACh-containing vesicles in response to nerve impulse activity but is assumed to be mediated by the high-affinity choline uptake system. The intensity of non-quantal ACh release in the myocardium correlates with the degree of manifestation of the effects of acetylcholinesterase inhibitors inducing the accumulation of non-quantal ACh in the myocardium. The present study deals with the influence of putative modulators of non-quantal ACh release: nitric oxide (NO) and ATP, on the intensity of cholinergic effects induced by organophosphorous acetylcholinesterase inhibitor paraoxon. Intracellular registration of bioelectrical activity in isolated right atrium preparations from rats was used. Under normal conditions, paraoxon (10^?7–10^?5 M) induced a marked decrease in the action potential (AP) duration at a level of 50 and 90% repolarization in the working right atrial myocardium and slowed down the sinus rhythm. ATP, which is known to suppress nonquantal ACh release in the neuromuscular junction, did not induce significant reduction or augmentation of the effects of paraoxon (5 × 10^?6 M). The NO donors, sodium nitroprusside (10^?5 M) and SNAP (10^?4 M), significantly reduced the paraoxon-induced AP shortening. Moreover, sodium nitroprusside decreased the negative chronotropic effect of paraoxon by 43.7%. On the contrary, NO synthase inhibitor L-NAME (10^?4 M), which is known to suppress endogenous NO production, augmented the AP shortening caused by paraoxon. It may be deduced that NO is a universal regulator of non-quantal ACh release intensity both in the myocardium and in the neuromuscular junction.     

Development of the caudate nucleus of rats in postnatal ontogenesis and formation of cholinergic mediation in it]

Morphological maturation of the rat's caudate nucleus and formation of cholinergic system in it were studied in postnatal ontogenesis. Under investigation were newborn rats, 7, 14, 21 day old rats and adult animals. The growth and maturation of the caudate nucleys were most intesne during the first two postnatal weeks, it was somewhat descreased by the beginning of the third week and continued in later terms as well. The structure of dendrites and axons became complicated during the first two weeks, the axo-dendritic contacts being also formed. The neuron structure in 14 days old rats was similar to that of adult animals. The activity of acetylcholinesterase in the caudate nucleus of 7 and 14 days rats was not great. It sharply increased by the 17th day and reached the level of adults with 3 weeks after birth. Possible correlations of the morpho-chemical maturation of the caudate nucleus and formation of motor activity in rats is discussed.     

Ontogenic differentiation of pig atrial and ventricular myosin

Myosin was isolated from pig atrial and ventricular myocardium during postnatal development and Ca2+-ATPase was determined and myosin light chains were analysed by electrophoresis in sodium dodecylsulfate polyacrylamide gel. During ontogenesis ATPase activity of ventricular myosin remains virtually unchanged, whereas that of atrial myosin increases. The patterns of myosin light chains of atrial and ventricular myosin differ from each other, but the individual pattern remains unchanged during the development.     

Changes in histones and transcription in the nuclei of sympathetic neurons in rats of various ages under the action of testosterone

A study of chromatin in KSTG neurocytes revealed the most remarkable changes of template activity after testosterone administration in 9 days old rats and less significant changes in adult rats. No changes were detected in 19 days old rats. The pattern of silver staining of the nuclei did not differ from the control in all age groups. The possible role of testosterone in differentiation of KSTG neurocytes in early postnatal period as well as the stage-related differences in mechanisms of the hormone action during ontogenesis are discussed.     

Influence of a period of inactivity on the duration of post-rest action potentials of the mammalian working ventricular myocardium in correlation to the preceding stimulation frequency

Experiments were carried out on the working right ventricular myocardium of adult cats, guinea-pigs and rabbits. Membrane voltage was recorded by the glass microelectrode technique and the preparations were stimulated with frequencies of 5, 1 and 0.2 Hz. After a steady state had been reached, a pause (TP) lasting 10-600 s was interpolated. The influence of TP on the duration (D) of post-rest action potentials (AP) was studied; the effect of the pause was measured at electric zero level (D0) and at further repolarization levels (-20, -40 and -60 mV, given here as D-20, D-40 and D-60). At 1 and 0.2 Hz frequency, the cat myocardium displayed lengthening of the AP proportional to the duration of the pause; at 5 Hz frequency, D0 reacted by lengthening up to TP = 120 s and to further pauses by slight shortening. D-60, at all frequencies, lengthened throughout the whole of the given TP range. The rabbit myocardium, at all the given frequencies, reacted up to TP = 60-120 s by marked shortening of post-rest AP at all repolarization levels; with longer pauses the AP lengthened. At 5 Hz frequency the guinea-pig myocardium reacted similarly to the cat myocardium; at the lower stimulation frequencies, the pause-induced changes in the post-rest AP were less strongly expressed. In all the given types of myocardium, the most pronounced post-rest AP reactions were those at electric zero level (the plateau phase of the AP); towards more negative repolarization values and with lower pre-pause stimulation frequencies they were less strongly expressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hypokinesia and muscle training on catecholamine levels of the myocardium of rats in postnatal ontogeny

Following muscular training and hypokinesia in postnatal ontogenesis (10 weeks) rats were examined by fluorometry for the content of catecholamines at rest and after extreme exertion (swimming). Regular muscular training led to an increase in catecholamine concentration in the myocardium. Hypokinesia decelerated catecholamine accumulation by the myocardium. A single extreme swimming exercise brought about a decrease in catecholamine concentration in the myocardium. The minimal adrenaline concentration was the same, being equal to 0.04 microgram/g crude tissue whatever the age and locomotion pattern.     

Species comparison of adenosine A1 receptors in isolated mammalian atrial and ventricular myocardium

Various species have been used as models to study the effects of adenosine (ADO) on atrial and ventricular myocardium, but few direct tissue comparisons between species have been made. This study further characterizes adenosine A(1) receptor binding, adenylate cyclase activity and direct and indirect A(1) receptor-mediated functional activity in atrial and ventricular tissue from Sprague-Dawley rats and Hartley guinea pigs. Rat right atria (RA) were found to be significantly more sensitive to cyclopentyladenosine (CPA), while guinea pig left atria (LA) were more sensitive to CPA. After the addition of isoproterenol (ISO), the reduction of CPA response in rat RA was significantly greater than in guinea pig; however, after ISO treatment, the guinea pig LA was more sensitive to CPA than the rat. Adenylate cyclase inhibition by CPA was significantly greater in atria and ventricles obtained from guinea pig than rat. In competition binding experiments, guinea pig RA had significantly more high affinity sites than rat, but the K(i)s were not significantly different. There were no significant differences between guinea pig LA and rat LA. Guinea pig ventricular tissue had fewer high affinity sites than rat without any differences in their K(i) values. In antagonist saturation experiments, the density and affinity of A(1) receptors in guinea pig cardiac membranes were significantly greater than in rat. Our results indicate definite species differences as well as tissue differences between rat and guinea pig. These differences must be considered when interpreting studies using rat and guinea pig tissue as models for cardiac function.     

Selective contractile dysfunction of left,not right,ventricular myocardium in the SHHF rat

The progression of hypertension to cardiac failure involves systemic changes that may ultimately affect contractility throughout the heart. Spontaneous hypertensive heart failure (SHHF) rats have depressed left ventricular (LV) function, but right ventricular (RV) dysfunction is less well characterized. Ultrathin (87 +/- 5 mircom) trabeculae were isolated from end-stage failing SHHF rats and from age-matched controls. Under near-physiological conditions (1 mM Ca(2+), 37 degrees C, 4 Hz), developed force (in mN/mm(2)) was not significantly different in SHHF LV and RV trabeculae and those of controls. SHHF LV preparations displayed a negative force-frequency behavior (40 +/- 7 vs. 23 +/- 4 mN/mm(2), 2 vs. 7 Hz); this relationship was positive in SHHF RV preparations (27 +/- 5 vs. 40 +/- 6 mN/mm(2)) and controls (32 +/- 6 vs. 44 +/- 9 mN/mm(2)). The response to isoproterenol (10(-6) M, 4 Hz) was depressed in SHHF LV preparations. The inotropic response to hypothermia was lost in SHHF LV trabeculae but preserved in SHHF RV trabeculae. Intracellular calcium measurements revealed impaired calcium handling at higher frequencies in LV preparations. We conclude that in end-stage failing SHHF rats, RV function is only marginally affected, whereas a severe contractile dysfunction of LV myocardium is present.     

Gamma- and UV-induced DNA synthesis in neurons of the rat neocortex

Nuclear DNA synthesis in neocortex neurons of neonatal 14- and 60-day rats after in vitro irradiation of isolated sections was estimated by the incorporation of a labeled precursor into DNA. gamma- and UV-radiation increased the rate of DNA synthesis in the cells of animals of all studied age groups. However, the level of the UV-induced synthesis sharply dropped during the postnatal ontogenesis while gamma-radiation-induced synthesis decreased slightly. The peculiarities revealed in the repair DNA synthesis seem to be influenced by the process of postnatal differentiation of a neuron accompanied by the nucleosome length shortening and the decrease in the DNA-polymerase alpha content.     

Development in ontogeny of the effect of ACTH fragment 4-7 on rat learning

Studies have been made of the effect of ACTH fragment 4-7 on learning in rats in early postnatal ontogenesis, as well as of the possibility of preservation of early learning during administration of this peptide to adult animals. It was shown that conditioned reaction of active avoidance practically cannot be formed in normal 13-15-day animals; however, administration of ACTH 4-7 increases the number of animals exhibiting adequate reactions. Weak effect of ACTH 4-7 in 12-15-day animals, in older ones (20-24 days) is changed by a significant stimulating effect.     

Effect of chronic stress during prepubertal period of life on development of inherited arterial hypertension

The immediate and long-lasting effects of environmental stress during prepubertal life on arterial blood pressure (AP) were studied in rats with inherited stress-induced arterial hypertension (ISIAH) and normotensive Wistar rats. Two models of chronic stress (the 21st-32nd postnatal days) were used: repeated handling and unpredictable stress of daily exposures to a variety of mild physical or psychoemotional stressors. Chronic prepubertal stress did not affect the basal or stress-induced AP levels in young or adult Wistar rats. In ISIAH rats, chronic stress during the early phase of hypertension development did not accelerate its formation and did not augment its manifestation in adults. Moreover, the basal AP was decreased in young and adult ISIAH rats exposed to prepubertal stress as compared to the age-matched controls. AP elevation under acute stress conditions was lower in young ISIAH rats exposed to unpredictable stress. No long-lasting effect of prepubertal stress on acute stress-induced AP elevation in adults was found. The conclusion was drawn that moderate physical and psychoemotional training at prehypertensive stage can positively affect the development of inherited arterial hypertension.     

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.     

Pharmacological sympatectomy changes heart's inotropic reaction on serotonin in postnatal ontogenesis of rats

In the present study, the influence of 0.1 microM, 1.0 microM, 10.0 microM serotonin (5-HT) on inotropic function (contraction force, time to peak force, time to relaxation) of desympathetized rats by guanethidine in postnatal ontogenesis was investigated. 5-HT has a positive inotropic effect on atria (178 %) and ventricles (122%) in 21-day old rats. In 21-day old desympathetized rats, serotonin influence on the atrium was depressed by 49 %, while ventricle contraction did not change. Atria contraction force in 100-day old rats increased by 38 %, while ventricle contraction force was decreased by 5-HT. In the 100-day old desympathetized rats, a significant elevation ofinotropic effect of 5-HT in atria by 91% and ventricles by 51% was revealed. It was shown that injection of guanethidine during three weeks since birth changes reaction on 5-HT in postnatal ontogenesis ofrats. In 21-day old desympathetized rats, 5-HT had a negative inotropic effect in the early period after pharmacological sympatectomy, while in the period of compensation the elevation of the positive inotropic effect of 5-HT occurred. Positive inotropic effect of atria in 100-day old desympathetized rats was twice as high as in control group. Our data suggest that there exists an interaction between adrenergic and 5-HT regulation in postnatal ontogenesis of rats.     

Differential modulation of right ventricular strain and right atrial mechanics in mild vs. severe pressure overload

Increased right atrial (RA) and ventricular (RV) chamber volumes are a late maladaptive response to chronic pulmonary hypertension. The purpose of the current investigation was to characterize the early compensatory changes that occur in the right heart during chronic RV pressure overload before the development of chamber dilation. Magnetic resonance imaging with radiofrequency tissue tagging was performed on dogs at baseline and after 10 wk of pulmonary artery banding to yield either mild RV pressure overload (36% rise in RV pressure; n = 5) or severe overload (250% rise in RV pressure; n = 4). The RV free wall was divided into three segments within a midventricular plane, and circumferential myocardial strain was calculated for each segment, the septum, and the left ventricle. Chamber volumes were calculated from stacked MRI images, and RA mechanics were characterized by calculating the RA reservoir, conduit, and pump contribution to RV filling. With mild RV overload, there were no changes in RV strain or RA function. With severe RV overload, RV circumferential strain diminished by 62% anterior (P = 0.04), 42% inferior (P = 0.03), and 50% in the septum (P = 0.02), with no change in the left ventricle (P = 0.12). RV filling became more dependent on RA conduit function, which increased from 30 ± 9 to 43 ± 13% (P = 0.01), than on RA reservoir function, which decreased from 47 ± 6 to 33 ± 4% (P = 0.04), with no change in RA pump function (P = 0.94). RA and RV volumes and RV ejection fraction were unchanged from baseline during either mild (P > 0.10) or severe RV pressure overload (P > 0.53). In response to severe RV pressure overload, RV myocardial strain is segmentally diminished and RV filling becomes more dependent on RA conduit rather than reservoir function. These compensatory mechanisms of the right heart occur early in chronic RV pressure overload before chamber dilation develops.     

Characteristics of Basic Parameters of the Hormonal Function of the Adrenal Cortex and Its Modification in Rat Ontogenesis

The stress-reactivity of the pituitary-adrenocortical system (PAS) as assessed by the dynamics of the blood corticosterone level changes was studied in rats administered with cortisol at different periods of their pre- and postnatal ontogenesis. The participation of the activation and deactivation mechanisms in this process was estimated by means of a mathematical modeling, using the basic parameters of hormonal wave. It is established that in the one-month old rat pups born from mothers injected with cortisol from the day 14 to 18 of pregnancy, the basal and stress-evoked PAS activity was not essentially changed, whereas the adult animals demonstrated a faster decrease of the stress-induced corticosterone level. Injection of cortisol at the early neonatal ontogenesis (1–5 day of life) decreased the basal and stress-induced corticosterone levels at the morning hours in one-month old rats, whereas in adult rats it increased the PAS stress-reactivity. Injection of cortisol in the late neonatal ontogenesis, i.e., during the period of formation of the sensory systems (opening of the ears, eyes, maximal motor activity) resulted predominantly in changing the time of completion of the stress-induced hormonal response that became longer than in control animals of the same age. With the aid of mathematical modeling, we have found that at the early neonatal period of development the hormonal exposure mainly increases the rate of PAS activation, whereas injection of glucocorticoids at the late neonatal period changes PAS regulation by a feedback mechanism, thus decreasing the rate of system inactivation and increasing the time of completion of PAS stress-induced reaction. It is concluded that the phenotypic reorganization of PAS stress-reactivity by exogenous corticosteroids depends on the time of their action on development of the excitatory and inhibitory mechanisms during the critical periods of their formation.     

Change of the neocortex nervous tissue in rat ontogenesis after hypoxia at various terms of embryogenesis

The performed study has shown that in rats submitted to hypoxia (3 h, 7% O2) at the 14th day of embryogenesis (E14) as compared with control animals, density of disposition of cells in the brain cortex decreased for the first month of postnatal ontogenesis (maximally by 40.8% by P20). In dying neurons, swelling of the cell body, lysis of organoids, and disturbance of the cytoplasmic membrane intactness were observed. Two waved of neuronal death by the mechanism of caspase-dependent apoptosis were revealed; the first involved large pyramidal neurons of the V layer (P10-20), the second--small pyramidal and non-pyramidal neurons of the II--III layers (P20-30). In neuropil of molecular layer, a decrease of the mean amount of labile synaptopodin-positive dendrite spines was observed, as compared with control. In rats exposed to hypoxia at E18, no changes of cell composition and structure of the nervous tissue were found in the studied brain cortex areas. Thus, formation of the cortex nervous tissue in postnatal ontogenesis of rats submitted to hypoxia at the period of neuroblast proliferation-migration is accompanied not only by a change of the cell composition of various cortex layers in early ontogenesis, but also by a decrease of the number of the synaptopodin-positive spines in molecular layer, the decrease being preserved in adult animals.