Voluntary exercise training restores anticontractile effect of NO in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism.

INTRODUCTION: Our recent study showed that NO-mediated anticontractile effect of endothelium is absent in coronary arteries of adult rats, which suffered from antenatal/early postnatal hypothyroidism. This study tested the hypothesis that exercise training would improve such detrimental consequences of early thyroid deficiency. DESIGN AND METHODS: Wistar dams received propylthiouracil (PTU, 7 ppm) in drinking water during gestation and two weeks postpartum; control dams received tap water. Six-week-old male offspring of control (CON) and PTU dams was divided into sedentary (CON-Sed, n = 12; PTU-Sed, n = 10) and trained (CON-Tr, n = 12; PTU-Tr, n = 10) groups; the latter had 24-h access to running wheels. Eight weeks later coronary arteries were studied by wire myography. Anticontractile effect of NO was assessed by the effects of NOS inhibitor L-NNA on the basal tone and contractile response to U46619. Oxidative phosphorylation complexes and eNOS were estimated by Western blotting. RESULTS: T3/T4 and TSH levels (ELISA) were normalized in the progeny of PTU-treated dams at the age of 6 weeks and were not affected by training. Total running distance did not differ between CON-Tr and PTU-Tr. The contents of oxidative phosphorylation complexes were increased post-training in triceps brachii muscle from CON-Tr and PTU-Tr and in heart from PTU-Tr. Coronary arteries of PTU-Sed compared to CON-Sed demonstrated higher basal tone and contractile response to U46619, which were not further increased by L-NNA. The effects of L-NNA on the basal tone and contractile response to U46619 did not differ in CON-Tr and PTU-Tr groups, but were elevated in PTU-Tr compared to PTU-Sed group. PTU-Tr rats in comparison to PTU-Sed group had higher eNOS content in heart. Responses of coronary arteries to DEA/NO did not differ among all experimental groups. CONCLUSIONS: Long-lasting coronary endothelial dysfunction resulted from transient thyroid deficiency during the antenatal/early postnatal period can be corrected by voluntary exercise training.

[THE INDICATORS OF GROWTH AND MYOGENESIS IN THE GLYCOLYTIC AND OXIDATIVE MUSCLES OF THE RAT AFTER INDIRECT ELECTROSTIMULATION].

A comparative analysis of the signaling pathways activity and gene expression in the red (RG) and white (WG) parts of the gastrocnemius muscle of rat after a series of short (1 s) tetanic contractions induced by motor nerve stimulation at a frequency of 100 Hz and with an amplitude that provides activation of all motor units of the muscle. WG compared to RG demonstrated a marked increase in the phosphorylation level of ERK1/2, although the increase in the phosphorylation of AMPK was not different in two muscles 2 h after the stimulation. Along with that, content of MyoD and myogenin mRNA in WG increased much higher than in RG, whereas the effect of stimulation on IGF-1, MaFbx and MuRF genes expression was weak and comparable in WG and RG. There was an increase of myostatin mRNA in RG. Thus, glycolytic muscle fibers of WG exhibit more pronounced regulatory shifts of hypertrophic character than oxidative muscle fibers of RG.

[Regional differences in the level of ERK1/2 phosphorylation and expression of the myogenic regulatory factors following electrostimulation with different mechanic and metabolic action on the gastrocnemius muscle].

Effect of high-frequency electrical stimulation of the sciatic nerve on ERK1/2 kinase phosphorylation and mRNA expression in MyoD (myogenic regulation factor) and myogenin in the red (RGM) and white (WGM) parts of the medial head in rat's m. gastrocnemius was studied. Two stimulation regimes were equalized both lengthwise and in total effort but differed in duration and number of contractions and, therefore, in mechanic and metabolic effects on the muscle. It was shown that growth of the number of phosphorylated ERK1/2 was particularly high in WCM due to application of the protocol for multiple short-time contractions. Whatever the stimulation regime, MyoD mRNA expression in RGM and WGM increases to the same extent, whereas myogenin mRNA expression does not change. Consequently, the regime with the predominantly mechanic effect is favorable to activation of the ERK signaling pathway in glycolytic myofibers.

[Changes of rat respiratory and locomotory muscles during aerobic exercise training in continuous and interval regimens].

Male Wistar rats were treadmill-trained for 8 weeks using one of the two regimens: with the constant running speed or with alternating high-speed and low-speed intervals. Both training regimens led to an increase of rat aerobic capacities and to a higher citrate synthase activity in the medial head of gastrocnemius muscle. No differences between the effects of two training regimens were observed. However, in contrast to constant-speed training the interval one resulted in myocardium hypertrophy and also in less pronounced changes in diaphragm muscle, such as slow-direction shift of myosin phenotype and reduction of muscle fiber cross-sectional area. Neither of the training regimens had an effect on corticosterone and thyroid hormones levels in rat blood, whereas the interval training resulted in a higher level of testosterone. Anabolic influence of testosterone during interval aerobic training may be favorable for heart hemodynamic capacity and force characteristics of the diaphragm.

[Dynamics of heart rate changes in rats following stepwise change of treadmill running speed].

Amplitude and temporal responses of heart rate to stepwise increase or decrease of treadmill running intensity were investigated in rats. Heart rate amplitude response was shown to be connected mainly with the change of sympathetic nervous activity whereas heart rate temporal response was shown to be determined predominantly by parasympathetic cardiotrophic influences.

[Comparative analysis of gene expression in rat locomotor muscles and diaphragm].

Gene expression profile in diaphragm in comparison to three principally different hindlimb muscles (soleus, red and white gastrocnemius) was studied using quantitative PCR. Expression levels of PGC-1alpha mRNA and myogenin mRNA in diaphragm were in accordance with its myosin phenotype and citrate synthase activity. However, diaphragm was characterised by atypically high content of MyoD mRNA as well as high content of IGF-1 mRNA and low content of myostatin mRNA. The latter two findings suggest high intensity of protein synthesis in diaphragm muscle fibers, although they have smaller cross sectional area than fibers in locomotor muscles.

[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.

Effect of aerobic training on innervation density and neurogenic responses of skin afferent blood vessels.

We studied the effect of 8-week aerobic training (treadmill running) on neurogenic responses and density of sympathetic innervation of subcutaneous artery in rats. In trained rats, the artery response to stimulation of intramural sympathetic nerve decreased, but the sensitivity of vascular smooth muscles to norepinephrine was not changed. The density of adrenergic nerve fibers in the arterial wall after training was also lower than in the control group. This effect of training can be explained by the need in increased heat emission during physical activity.

[Comparative analysis of vasomotor responses and sympathetic innervation of feed arteries from locomotor and respiratory muscles in a rat].

The characteristics of feeding arteries of diaphragm and medial gastrocnemius (with a diameter of 200-250 micron) were studied. The registration of the mechanical activity of ring preparations under isometric conditions revealed that diaphragm arteries, like arteries of other muscles with a high content of slow muscle fibers, are highly sensitive to adrenoceptor agonists and acetylcholine. The differences in endothelium-dependent relaxation between diaphragm and gastrocnemius arteries are preserved in the presence of L-NAME and diclofenac. Responses to serotonin in diaphragm and gastrocnemius arteries are similar. At the same time, the high density of innervation is characteristic of diaphragm artery only, while in other slow muscles it is low. The density of adrenergic fibers plexus in the diaphragm artery is much higher than in the gastrocnemius artery. The results suggest that the properties of small arteries of diaphragm are determined not only by the oxidative capacity of diaphragm muscle fibers but also by the belonging of the diaphragm to respiratory musculature.