Recent progress in angiotensin II type 2 receptor research in the cardiovascular system.
Angiotensin II (Ang II) plays an important role in regulating cardiovascular hemodynamics and structure. Multiple lines of evidence have suggested the existence of Ang II receptor subtypes, and at least 2 distinct receptor subtypes have been defined on the basis of their differential pharmacological and biochemical properties and designated as type 1 (AT1) and type 2 (AT2) receptors. To date, most of the known effects of Ang II in adult tissues are attributable to the AT1 receptor. Recent cloning of the AT2 receptor contributes to reveal its physiological functions, but many functions of the AT2 receptor are still an enigma. AT1 and AT2 receptors belong to the 7-transmembrane, G protein-coupled receptor family. However, accumulating evidence demonstrates that the function and signaling mechanisms of these receptor subtypes are quite different, and these receptors may exert opposite effects in terms of cell growth and blood pressure regulation. We will review the role of the AT2 receptor in the cardiovascular system and the molecular and cellular mechanisms of AT2 receptor action. (+info)
Cardiovascular and metabolic adaptations in horses competing in cross-country events.
The cardiovascular and metabolic response to two cross-country events (CC*: preliminary level and CC*** advanced level) were analysed in 8 male eventing horses (4 Anglo-Hunter and 4 Anglo-Arabian). This study focused on the establishment of the main metabolic pathways involved in the muscle energy resynthesis during the competitions. Heart rate (HR) was recorded throughout the CC events. Jugular venous blood samples were withdrawn before the warm-up period, immediately after the competitions and at 5 and 10 min in the recuperation period. The following haematological parameters were studied: red blood cells (RBC), packed cell volume (PCV), haemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC), and number and percentages of lymphocytes (LYM) and granulocytes and monocytes (GRAN). One fraction of blood was centrifuged and, in plasma, lactate (LA), total plasma protein (TPP) and the rate of LA disappearance were determined. The competitions induced significant increases in RBC, Hb, PCV, MCV and TPP. Plasma LA response exceeded the anaerobic threshold of 4 mmol/l, reaching a maximum level of 13.3 mmol/l. HR ranged from 140 to more than 200 bpm, peaking at 230 bpm, revealing a limitation in the oxygen supply to the working muscles. It was concluded that muscle energy resynthesis during a CC event is provided both through oxidative processes and glycolysis with LA formation. Therefore, both stamina and power exercises are required for eventing horses. (+info)
Development of a 12-min treadmill walk test at a self-selected pace for the evaluation of cardiorespiratory fitness in adult men.
The direct measurement of true maximal oxygen uptake (VO2max) and oxygen uptake corresponding to anaerobic threshold (VO2AT) is not always practical, especially in middle age and older populations. Therefore, the purpose of this study was to develop a simple test that could accurately estimate cardiorespiratory fitness using a submaximal treadmill walking protocol for middle age, older, sedentary individuals and patients with chronic disease. Subjects for this study were 42 men (44.9 +/- 15.7 years), which included 17 patients with coronary heart disease (57.0 +/- 9.6 years). VO2peak and VO2AT were measured using a treadmill protocol (VO2peak; 38.4 +/- 11.6 ml/kg/min, VO2AT; 22.9 +/- 7.4 ml/kg/min). This simple test assessed the total distance covered in 12 minutes on the treadmill at an intensity corresponding to either 1) 11 on the Borg scale of ratings of perceived exertion (RPE11), 2) 13 on the Borg scale of ratings of perceived exertion (RPE13), or 3) "Optimal" by subjective judgment. The correlation coefficients between VO2peak or VO2AT and total distance at the three intensities (RPE11; 950 +/- 100 m, RPE13; 1080 +/- 140 m Optimal; 1050 +/- 110 m) were statistically significant, ranging from 0.72 to 0.85. The test-retest reliability coefficient on 12 subjects was 0.98. The oxygen uptake (VO2) was measured during the three walk tests on 15 subjects. There were no significant changes in submaximal VO2 values from min 4 to min 12 (RPE11; 19.8 +/- 4.7 ml/kg/min, RPE13; 24.1 +/- 4.9 ml/kg/min, Optimal; 23.1 +/- 4.8 ml/kg/min) in any of the three tests. Similarly, the three submaximal VO2 values did not differ from the VO2AT value (21.2 +/- 8.3 ml/kg/min) obtained in the initial maximal test. These results suggest that the 12-min submaximal treadmill walk test (STWT) is a valid method for the assessment of VO2peak and VO2AT. Therefore, the STWT could be a useful performance test for evaluating cardiorespiratory fitness in middle age, older, sedentary individuals and patients with chronic disease. (+info)
Effect of working hours on cardiovascular-autonomic nervous functions in engineers in an electronics manufacturing company.
A field survey of 147 engineers (23-49 years) in an electronics manufacturing company was conducted to investigate the effect of working hours on cardiovascular-autonomic nervous functions (urinary catecholamines, heart rate variability and blood pressure). The subjects were divided into 3 groups by age: 23-29 (n = 49), 30-39 (n = 74) and 40-49 (n = 24) year groups. Subjects in each age group were further divided into shorter (SWH) and longer (LWH) working hour subgroups according to the median of weekly working hours. In the 30-39 year group, urinary noradrenaline in the afternoon for LWH was significantly lower than that for SWH and a similar tendency was found in the LF/HF ratio of heart rate variability at rest. Because these two autonomic nervous indices are related to sympathetic nervous activity, the findings suggested that sympathetic nervous activity for LWH was lower than that for SWH in the 30-39 year group. Furthermore, there were significant relationships both between long working hours and short sleeping hours, and between short sleeping hours and high complaint rates of "drowsiness and dullness" in the morning in this age group. Summarizing these results, it appeared that long working hours might lower sympathetic nervous activity due to chronic sleep deprivation. (+info)
Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic cardiovascular regulation.
1. The aim of the present study was to analyse the cardiovascular actions of the synthetic CB1/CB2 cannabinoid receptor agonist WIN55212-2, and specifically to determine its sites of action on sympathetic cardiovascular regulation. 2. Pithed rabbits in which the sympathetic outflow was continuously stimulated electrically or which received a pressor infusion of noradrenaline were used to study peripheral prejunctional and direct vascular effects, respectively. For studying effects on brain stem cardiovascular regulatory centres, drugs were administered into the cisterna cerebellomedullaris in conscious rabbits. Overall cardiovascular effects of the cannabinoid were studied in conscious rabbits with intravenous drug administration. 3. In pithed rabbits in which the sympathetic outflow was continuously electrically stimulated, intravenous injection of WIN55212-2 (5, 50 and 500 microg kg(-1)) markedly reduced blood pressure, the spillover of noradrenaline into plasma and the plasma noradrenaline concentration, and these effects were antagonized by the CB1 cannabinoid receptor-selective antagonist SR141716A. The hypotensive and the sympathoinhibitory effect of WIN55212-2 was shared by CP55940, another mixed CB1/CB2 cannabinoid receptor agonist, but not by WIN55212-3, the enantiomer of WIN55212-2, which lacks affinity for cannabinoid binding sites. WIN55212-2 had no effect on vascular tone established by infusion of noradrenaline in pithed rabbits. 4. Intracisternal application of WIN55212-2 (0.1, 1 and 10 microg kg(-1)) in conscious rabbits increased blood pressure and the plasma noradrenaline concentration and elicited bradycardia; this latter effect was antagonized by atropine. 5. In conscious animals, intravenous injection of WIN55212-2 (5 and 50 microg kg(-1)) caused bradycardia, slight hypotension, no change in the plasma noradrenaline concentration, and an increase in renal sympathetic nerve firing. The highest dose of WIN55212-2 (500 microg kg(-1)) elicited hypotension and tachycardia, and sympathetic nerve activity and the plasma noradrenaline concentration declined. 6. The results obtained in pithed rabbits indicate that activation of CB1 cannabinoid receptors leads to marked peripheral prejunctional inhibition of noradrenaline release from postganglionic sympathetic axons. Intracisternal application of WIN55212-2 uncovered two effects on brain stem cardiovascular centres: sympathoexcitation and activation of cardiac vagal fibres. The highest dose of systemically administered WIN55212-2 produced central sympathoinhibition; the primary site of this action is not known. (+info)
Cardiopulmonary responses of middle-aged men without cardiopulmonary disease to steady-rate positive and negative work performed on a cycle ergometer.
BACKGROUND AND PURPOSE: Understanding physiological responses to negative work allows therapists to be more knowledgeable when they prescribe this form of exercise. The physiological responses of 12 men without cardiopulmonary disease, aged 39 to 65 years (X=49.7, SD=9.3), to negative work (eccentric muscle contractions) and to positive work (concentric muscle contractions) were compared. SUBJECTS AND METHODS: Subjects performed the 2 types of work on a motorized cycle ergometer at pedaling frequencies of 35, 55, and 75 rpm with a constant power output of 60 W. Steady-rate values of oxygen consumption (VO2), heart rate (HR), minute ventilation (VE), tidal volume (VT), and breathing frequency (fb) were obtained during 6 test conditions (positive and negative work at each of the 3 pedaling frequencies). RESULTS: Values for all measures were greater during positive work than during negative work, except for fb. During positive work, values for all variables were greatest at 75 rpm, except for fb. During negative work, VO2 and HR were greater at 75 and 35 rpm than at 55 rpm, and VE and VT were greater at 75 rpm than at 55 rpm. Breathing frequency was not different among pedaling frequencies. CONCLUSION AND DISCUSSION: The results confirmed that negative work performed on a cycle ergometer is associated with low metabolic cost in older men without cardiopulmonary disease. Although VE was determined primarily by changes in VT during negative work, a comparable disproportionate increase in fb was observed at the start of negative work. Such changes in breathing patterns have implications for the prescription of negative work for patients with lung disease. (+info)
Systemic administration of lipopolysaccharide induces release of nitric oxide and glutamate and c-fos expression in the nucleus tractus solitarii of rats.
There is increasing recognition that communication pathways exist between the immune system and brain, which allows bidirectional regulation of immune and brain responses to infection. The endotoxin lipopolysaccharide (LPS) has been reported to elicit release of cytokines and expression of inducible nitric oxide synthase (iNOS) in peripheral organs. Whereas LPS given systemically causes endotoxic shock, little is known about its central nervous system action, particularly the induction of iNOS. Nitric oxide (NO) and glutamate in the nucleus tractus solitarii (NTS) are important mediators of central cardiovascular regulation. We have previously demonstrated that intravenous injections of LPS increased the NO precursor L-arginine-induced depressor effect in the NTS. The present study investigated further the effects of LPS on the release of NO and glutamate in the NTS and the expression of c-fos, an immediate early response gene product, in neural substrates for central cardiovascular control. In vivo microdialysis coupled with chemiluminescence and electrochemical detection techniques were used to measure extracellular levels of NO and glutamate in the rat NTS. Immunohistochemistry was used for the examination of c-fos protein expression. We found that intravenous infusion of LPS (10 mg/kg) produced a biphasic depressor effect, with an early, sharp hypotension that partially recovered in 15 minutes and a secondary, more prolonged hypotension. In the NTS, a progressive increase of extracellular glutamate and NO levels occurred 3 and 4 hours after LPS was given, respectively. The effects of LPS on the induction of delayed hypotension and NO formation in the NTS were abolished by pretreatment with the iNOS inhibitor aminoguanidine. Finally, c-fos protein expression in the NTS and related structures for cardiovascular regulation was observed after LPS challenge. Taken together, these data suggest that an endotoxin given systemically can elicit delayed increases of glutamate release and iNOS-dependent NO production in the NTS and activate the central neural pathway for modulating cardiovascular function. (+info)
Variation in physical fitness between ethnic groups in nine year olds.
BACKGROUND: There is little information on cardio-respiratory fitness of children, especially in ethnic minorities in Britain. In this study we assess the associations of social factors, ethnicity, parental health related factors, child's anthropometry, blood pressure and cholesterol measurements with cardio-respiratory fitness. METHODS: Power output against load at 85% of the maximum heart rate (PWC85%), was measured, using a cycle-ergometer test, in children aged 8-9 years in 22 randomly selected areas in England, 14 in Scotland and in 20 inner city areas in England. The subjects were 317 boys and 310 girls from the English sample, 152 boys and 140 girls from the Scottish sample and 242 boys and 261 girls from the inner city sample. RESULTS: Short stature (P < 0.001), fatness (P < 0.001), and Indian subcontinent origin (OR = 0.34, 95% CI: 0.16, 0.68 in boys and OR = 0.22, 95% CI: 0.12, 0.40 in girls) were associated with inability to finish the test. In those who finished the test PWC85% was greater in taller children and in those with lower skinfold values (P < 0.001, except height in boys P = 0.017). The PWC85% in those originating in the Indian continent was lower (-0.17 watt/kg, 95% CI :-0.32, -0.01 in boys and -0.29, 95% CI: -0.43, -0.14 in girls) than in white children. CONCLUSIONS: Shorter and obese children have poorer physical fitness than other children. Physical fitness is lower in children originating in the Indian subcontinent than other British children. This seems to be unrelated to socioeconomic disadvantage. Physical inactivity and lack of cycling skills may explain our findings. (+info)