Brain-derived neurotrophic factor (BDNF) has an important role in regulating maintenance, growth and survival of neurons. However, the main source of circulating BDNF in response to exercise is unknown. To identify whether the brain is a source of BDNF during exercise, eight volunteers rowed for 4 h while simultaneous blood samples were obtained from the radial artery and the internal jugular vein. To further identify putative cerebral region(s) responsible for BDNF release, mouse brains were dissected and analysed for BDNF mRNA expression following treadmill exercise. In humans, a BDNF release from the brain was observed at rest ( P < 0.05), and increased two- to threefold during exercise ( P < 0.05). Both at rest and during exercise, the brain contributed 70â80% of circulating BDNF, while that contribution decreased following 1 h of recovery. In mice, exercise induced a three- to fivefold increase in BDNF mRNA expression in the hippocampus and cortex, peaking 2 h after the termination of exercise. These results suggest that the brain is a major but not the sole contributor to circulating BDNF. Moreover, the importance of the cortex and hippocampus as a source for plasma BDNF becomes even more prominent in response to exercise.
We hypothesized that training with eccentric contractions only (therefore using higher loads) would yield greater muscle structural and strength gains compared with conventional resistance training. Nine older adults (mean Â± s.d. age, 74 Â± 3 years) were assigned to a conventional (CONV) resistance training group performing both concentric and eccentric contractions and 10 (age, 67 Â± 2 years) to an eccentric-only (ECC) resistance training group. Both groups trained three times per week for 14 weeks at 80% of the five-repetition maximum, specific to each training mode. Maximal knee extensor torque was assessed during isometric, concentric and eccentric contractions across a range of angular velocities (0â3.49 rad s â1 ). Vastus lateralis muscle architecture (fascicle length, pennation angle and muscle thickness) was assessed in vivo at rest using ultrasonography. Training increased fascicle length in both groups, but the increase was significantly greater in the ECC (20% increase) than the CONV group (8% increase). Conversely, pennation angle significantly increased in the CONV (35% increase) but not in the ECC group (5% increase). Muscle thickness increased to a similar extent in both groups (â¼12% increase). In the ECC group, eccentric knee extensor torque increased by 9â17% across velocities, but concentric torque was unchanged. Conversely, in the CONV group, concentric torque increased by 22â37% across velocities, but eccentric torque was unchanged. Instead, isometric torque increased to a similar extent in both groups (â¼8% increase). Thus, the two training regimens resulted in differential adaptations in muscle architecture and strength. These results suggest that the stimulus for adding sarcomeres in-series and in-parallel may be different, which implies that different myogenic responses were induced by the two different training methods.
Computational models of cardiac electrophysiology are exemplar demonstrations of the integration of multiple data sets into a consistent biophysical framework. These models encapsulate physiological understanding to provide quantitative predictions of function. The combination or extension of existing models within a common framework allows integrative phenomena in larger systems to be investigated. This methodology is now routinely applied, as demonstrated by the increasing number of studies which use or extend previously developed models. In this study, we present a meta-analysis of this model re-use for two leading models of cardiac electrophysiology in the form of parameter inheritance trees, a sensitivity analysis and a comparison of the functional significance of the sodium potassium pump for defining restitution curves. These results indicate that even though the models aim to represent the same physiological system, both the sources of parameter values and the function of equivalent components are significantly different.
In mammals, including man, epidemiological and experimental studies have shown that a range of environmental factors acting during critical periods of early development can alter adult phenotype. Hormones have an important role in these epigenetic modifications and can signal the type, severity and duration of the environmental cue to the developing feto-placental tissues. They affect development of these tissues both directly and indirectly by changes in placental phenotype. They act to alter gene expression, hence the protein abundance in a wide range of different tissues, which has functional consequences for many physiological systems both before and after birth. By producing an epigenome specific to the prevailing condition in utero , hormones act as epigenetic signals in developmental programming, with important implications for adult health and disease. This review examines the role of hormones as epigenetic signals by considering their responses to environmental cues, their effects on phenotypical development and the molecular mechanisms by which they programme feto-placental development, with particular emphasis on the glucocorticoids.
Adenosine 5â²-triphosphate (ATP) is a cotransmitter with classical transmitters in most nerves in the peripheral and central nervous systems, although the proportions vary between tissues and species and in different developmental and pathophysiological circumstances. There was early evidence that ATP was released together with acetylcholine (ACh) from motor nerves supplying skeletal muscle, although it was considered at the time as a molecule involved in the vesicular uptake and storage of ACh. Later it was shown that in the developing neuromuscular junction, released ATP acted on P2X receptor ion channels as a genuine cotransmitter with ACh. Adenosine triphosphate was shown to be released from sympathetic nerves supplying the guinea-pig taenia coli in 1971. Soon after, the possibility was raised that ATP was coreleased with noradrenaline from sympathetic nerves to guinea-pig seminal vesicle, cat nictitating membrane and guinea-pig vas deferens. Sympathetic purinergic cotransmission has also been demonstrated in many blood vessels. Parasympathetic nerves supplying the urinary bladder use ACh and ATP as cotransmitters; ATP acts through P2X ionotropic receptors, whereas the slower component of the response is mediated by the metabotropic muscarinic receptor. Adenosine triphosphate and glutamate appear to be cotransmitters in primary afferent sensory neurons. Adenosine triphosphate, calcitonin gene-related peptide and substance P coexist in some sensory-motor nerves. A subpopulation of intramural enteric nerves provides non-adrenergic, non-cholinergic inhibitory innervation of gut smooth muscle. Three cotransmitters are involved, namely ATP, nitric oxide and vasoactive intestinal polypeptide. In recent years, studies have shown that ATP is released with ACh, noradrenaline, glutamate, Î³-aminobutyric acid, 5-hyroxytryptamine and dopamine in different subpopulations of neurons in the central nervous system.
In the present study, we evaluated the mechanisms underpinning the hypertension observed in freely moving juvenile rats submitted to chronic intermittent hypoxia (CIH). Male juvenile Wistar rats (20â21 days old) were submitted to CIH (6% O 2 for 40 s every 9 min, 8 h day â1 ) for 10 days while control rats were maintained in normoxia. Prior to CIH, baseline systolic arterial pressure (SAP), measured indirectly, was similar between groups (86 Â± 1 versus 87 Â± 1 mmHg). After exposure to CIH, SAP recorded directly was higher in the CIH ( n = 28) than in the control group ( n = 29; 131 Â± 3 versus 115 Â± 2 mmHg, P < 0.05). This higher SAP of CIH rats presented an augmented power of oscillatory components at low (10.05 Â± 0.91 versus 5.02 Â± 0.63 mmHg 2 , P < 0.05) and high (respiratory-related) frequencies (12.42 Â± 2.46 versus 3.28 Â± 0.61 mmHg 2 , P < 0.05) in comparison with control animals. In addition, rats exposed to CIH also exhibited an increased cardiac baroreflex gain (â3.11 Â± 0.08 versus â2.1 Â± 0.10 beats min â1 mmHg â1 , P < 0.0001), associated with a shift to the right of the operating point, in comparison with control rats. Administration of hexamethonium (ganglionic blocker, i.v. ), injected after losartan (angiotensin II type 1 receptor antagonist) and [Î²-mercapto-Î²,Î²-cyclopenta-methylenepropionyl 1 , O -Me-Tyr 2 , Arg 8 ]-vasopressin (vasopressin type 1a receptor antagonist), produced a larger depressor response in the CIH ( n = 8) than in the control group ( n = 9; â49 Â± 2 versus â39 Â± 2 mmHg, P < 0.05). Fifteen days after the cessation of exposure to CIH, the mean arterial pressure of CIH rats returned to normal levels. The data indicate that the sympathetic-mediated hypertension observed in conscious juvenile rats exposed to CIH is not secondary to a reduction in cardiac baroreflex gain and exhibits a higher respiratory modulation, indicating that an enhanced respiratoryâsympathetic coupling seems to be the major factor contributing to hypertension in rats exposed to CIH.
The aim of this study was to determine the applicability and reliability of a transcranial magnetic stimulation twitch interpolation technique for measuring voluntary activation of a lower limb muscle group. Cortical voluntary activation of the knee extensors was determined in nine healthy men on two separate visits by measuring superimposed twitch torques evoked by transcranial magnetic stimulation during isometric knee extensions of varying intensity. Superimposed twitch amplitude decreased linearly with increasing voluntary torque between 50 and 100% of mean maximal torque, allowing estimation of resting twitch amplitude and subsequent calculation of voluntary activation. There were no systematic differences for maximal voluntary activation within day (mean Â± s.d. 90.9 Â± 6.2 versus 90.7 Â± 5.9%; P = 0.98) or between days (90.8 Â± 6.0 versus 91.2 Â± 5.7%; P = 0.92). Systematic bias and random error components of the 95% limits of agreement were 0.23 and 9.3% within day versus â0.38 and 7.5% between days. Voluntary activation was also determined immediately after a 2 min maximal voluntary isometric contraction; in four of these subjects, voluntary activation was determined 30 min after the sustained contraction. Immediately after the sustained isometric contraction, maximal voluntary activation was reduced from 91.2 Â± 5.7 to 74.2 Â± 12.0% ( P < 0.001), indicating supraspinal fatigue. After 30 min, voluntary activation had recovered to 85.4 Â± 8.8% ( P = 0.39 versus baseline). These results demonstrate that transcranial magnetic stimulation enables reliable measurement of maximal voluntary activation and assessment of supraspinal fatigue of the knee extensors.
The enzymes required for aldosterone synthesis from cholesterol are expressed in rat and human brains. The hypertension of Dahl salt-sensitive (SS) rats is mitigated by the intracerebroventricular ( i.c.v .) infusion of antagonists of the mineralocorticoid receptor (MR) and downstream effectors of mineralocorticoid action, as well as ablations of brain areas that also abrogate mineralocorticoidâsalt excess hypertension in normotensive rats. We used real time RT-PCR to measure mRNA of aldosterone synthase and 11Î²-hydroxylase, the requisite enzymes for the last step in the synthesis of aldosterone and corticosterone, respectively, MR and the determinants of MR ligand specificity, 11Î²-hydroxysteroid dehydrogenase types 1 and 2 (11Î²-HSD1&2) and hexose-6-phosphate dehydrogenase (H6PDH). A combination of extraction and ELISA was used to measure aldosterone concentrations in tissue and urine of SS and SpragueâDawley (SD) rats. Aldosterone synthase mRNA expression was higher in the brains and lower in the adrenal glands of SS compared with SD rats. The amounts of mRNA for MR, 11Î²-hydroxylase, 11Î²-HSD1&2 and H6PD were similar. Aldosterone concentrations were greater in brains of SS than SD rats, yet, in keeping with the literature, the circulating and total aldosterone production of aldosterone in SS rats were not. The selective inhibitor of aldosterone synthase, FAD286, was infused i.c.v . or subcutaneously in a cross-over blood pressure study in hypertensive SS rats further challenged by a high-salt diet. The i.c.v . infusion of FAD286, at a dose that had no effect systemically, significantly and reversibly lowered blood pressure in SS rats. Aldosterone synthesis in brains of SS rats is greater than in SD rats and is important in the genesis of their salt-sensitive hypertension.
Thrombospondin-1 (TSP-1) is a known inhibitor of angiogenesis; however, a skeletal muscle phenotype of TSP-1 null mice has not been investigated. The purposes of this study were to compare and contrast TSP-1 null and wild-type mice by examining the following: (1) capillarity in the skeletal and cardiac muscles; (2) fibre type composition and oxidative enzyme activity in the hindlimb; and (3) the consequences of TSP-1 gene deletion for exercise capacity. In TSP-1 null mice, maximal running speed was 11% greater and time to exhaustion during submaximal endurance running was 67% greater compared with wild-type mice. Morphometric analyses revealed that TSP-1 null mice had higher ( P < 0.05) capillarity in the heart and skeletal muscle than wild-type mice, whereas no differences for fibre type composition or oxidative enzyme activity were present between the two groups. Cardiac function, as measured by transthoracic echocardiography, revealed no difference in myocardial contractility but greater left ventricular end-diastolic and systolic dimensions, corresponding to an elevated heart mass in the TSP-1 null mice. The results of this study indicate that TSP-1 is an important endogenous negative regulator of angiogenesis that prevents excessive capillarization in the heart and skeletal muscles. The increased capillarity alone was sufficient to increase ( P < 0.05) exercise capacity. These data demonstrate that the capillary-to-muscle interface is a critical factor that limits oxygen transport during exercise.
With the publication in 1972 of a large computer model of circulatory control, Guyton and colleagues challenged the then prevailing views on how blood pressure and cardiac output were controlled. At that time, it was widely accepted that the heart controlled cardiac output and that peripheral resistance controlled arterial blood pressure. By incorporating the empirically demonstrated concepts of blood flow autoregulation and the pressureânatriuresis relationship into their mathematical model, Guyton and colleagues were able to develop a number of revolutionary concepts. Guyton's circulatory model was particularly instrumental in exploring the linkage between blood pressure and sodium balance and in demonstrating an overriding importance of renal salt and water balance in setting the long-term blood pressure level. In both the model and experimental data, any long-lasting imbalance between salt intake and salt excretion leads to a progressive alteration of the degree of filling of the vascular system and thus to parallel changes in blood pressure. In turn, changes in blood pressure alter sodium excretion, opposing the initial salt imbalance. Although Guyton's model does not include the most recent cardiovascular discoveries, the concepts underlying the basic functioning of the cardiovascular system can serve as a well-built basis for the development of new, large and integrative cardiovascular models.
The db / db mice serve as a good model for type 2 diabetes characterized by hyperinsulinaemia and progressive hyperglycaemia. There are limited and conflicting data on the cardiovascular changes in this model. The aim of the present study was to characterize the cardiovascular and autonomic phenotype of male db / db mice and evaluate the role of angiotensin II AT 1 receptors. Radiotelemetry was used to monitor 24 h blood pressure (BP) in mice for 8 weeks. Parameters measured were mean arterial pressure (MAP), heart rate (HR) and their variabilities. In 8-week-old db / db mice, the MAP and BP circadian rhythms were not different from age-matched control mice, while HR and locomotor activity were decreased. With ageing, MAP gradually increased in db / db mice, and the 12 h light values did not dip significantly from the 12 h dark periods. In 14-week-old mice, MAP was increased during light (101 Â± 1 versus 117 Â± 2 mmHg, P < 0.01; control versus db / db mice) and dark phases (110 Â± 1.7 versus 121 Â± 3.1 mmHg, P < 0.01; control versus db / db mice). This increase in MAP was associated with a significant increase in plasma angiotensin-converting enzyme activity and angiotensin II levels. Chronic treatment with losartan (10 mg kg â1 day â1 ) blocked the increase in MAP in db / db mice, with no effect in control animals. Spectral analysis was used to monitor autonomic cardiovascular function. The circadian rhythm observed in systolic arterial pressure variance and its low-frequency component in control mice was absent in db / db mice. There were no changes in HR variability and spontaneous baroreflex sensitivity between control and db / db mice. The results document an age-related increase in MAP in db / db mice, which can be reduced by antagonism of angiotensin II AT 1 receptors, and alterations in autonomic balance and components of the reninâangiotensin system.
Low-level laser (LLL) irradiation promotes proliferation of muscle satellite cells, angiogenesis and expression of growth factors. Satellite cells, angiogenesis and growth factors play important roles in the regeneration of muscle. The objective of this study was to examine the effect of LLL irradiation on rat gastrocnemius muscle recovering from disuse muscle atrophy. Eight-week-old rats were subjected to hindlimb suspension for 2 weeks, after which they were released and recovered. During the recovery period, rats underwent daily LLL irradiation (GaâAlâAs laser; 830 nm; 60 mW; total, 180 s) to the right gastrocnemius muscle through the skin. The untreated left gastrocnemius muscle served as the control. In conjunction with LLL irradiation, 5-bromo-2â²-deoxyuridine (BrdU) was injected subcutaneously to label the nuclei of proliferating cells. After 2 weeks, myofibre diameters of irradiated muscle increased in comparison with those of untreated muscle, but did not recover back to normal levels. Additionally, in the superficial region of the irradiated muscle, the number of capillaries and fibroblast growth factor levels exhibited significant elevation relative to those of untreated muscle. In the deep region of irradiated muscle, BrdU-positive nuclei of satellite cells and/or myofibres increased significantly relative to those of the untreated muscle. The results of this study suggest that LLL irradiation can promote recovery from disuse muscle atrophy in association with proliferation of satellite cells and angiogenesis.
The aim of the present study was to assess the influence of body posture on post-submaximal exercise parasympathetic reactivation and to examine whether this influence was preserved under a heightened sympathetic background. On four occasions, eleven moderately trained subjects (22.1 Â± 3.0 years old) performed, in random order, two consecutive submaximal running bouts (CTs), each followed by 5 min passive recovery in an upright (Up), sitting (Sit), supine (Sup) or supine with legs up position (SupLu). Between both CTs, participants performed 150 s of supramaximal intermittent running (SI). Parasympathetic reactivation was assessed from heart rate recovery (HRR) and variability (HRV; e.g. rMSSD 30 s ) indices calculated during the 5 min recovery periods [i.e. before (N) and after SI (post-SI)]. In the N condition, Sup position was associated with a faster and greater increase in rMSSD 30 s than Sit and SupLu (both P < 0.01), which were all higher compared with Up ( P < 0.001). A âtimeâ effect was shown in Sit, Sup and SupLu (all P < 0.05), but not in Up ( P = 0.99). All N values were higher than post-SI values ( P < 0.001), except for Up, where a trend was apparent ( P = 0.06). In the post-SI condition, a position effect was preserved for HRR ( P < 0.001), but not for HRV indices ( P = 0.99 for rMSSD 30 s ). In conclusion, the supine position accelerated and increased parasympathetic reactivation more than the other three positions, but the posture effect was less evident following supramaximal exercise. In the context of an accentuated sympathetic background (i.e. post-SI), postexercise HRV indices are less gravity dependent than HRR, reflecting more the exercise-related changes in parasympathetic activity.
Sudden cardiac death is a major health problem in the industrialized world. The lethal event is typically ventricular fibrillation (VF), during which the co-ordinated regular contraction of the heart is overthrown by a state of mechanical and electrical anarchy. Understanding the excitation patterns that sustain VF is important in order to identify potential therapeutic targets. In this paper, we studied the organization of human VF by combining clinical recordings of electrical excitation patterns on the epicardial surface during in vivo human VF with simulations of VF in an anatomically and electrophysiologically detailed computational model of the human ventricles. We find both in the computational studies and in the clinical recordings that epicardial surface excitation patterns during VF contain around six rotors. Based on results from the simulated three-dimensional excitation patterns during VF, which show that the total number of electrical sources is 1.4 Â± 0.12 times greater than the number of epicardial rotors, we estimate that the total number of sources present during clinically recorded VF is 9.0 Â± 2.6. This number is approximately fivefold fewer compared with that observed during VF in dog and pig hearts, which are of comparable size to human hearts. We explain this difference by considering differences in action potential duration dynamics across these species. The simpler spatial organization of human VF has important implications for treatment and prevention of this dangerous arrhythmia. Moreover, our findings underline the need for integrated research, in which human-based clinical and computational studies complement animal research.
The aim of this study was to determine whether low-frequency whole-body vibration (WBV) modulates the excitability of the corticospinal and intracortical pathways related to tibialis anterior (TA) muscle activity, thus contributing to the observed changes in neuromuscular function during and after WBV exercise. Motor-evoked potentials (MEPs) elicited in response to transcranial magnetic stimulation (TMS) of the leg area of the motor cortex were recorded in TA and soleus (SOL) muscles of seven healthy male subjects whilst performing 330 s continuous static squat exercise. Each subject completed two conditions: control (no WBV) and WBV (30 Hz, 1.5 mm vibration applied from 111 to 220 s). Five single suprathreshold and five paired TMS were delivered during each squat period lasting 110 s (pre-, during and post-WBV). Two interstimulus intervals (ISIs) between the conditioning and the testing stimuli were employed in order to study the effects of WBV on short-interval intracortical inhibition (SICI, ISI = 3 ms) and intracortical facilitation (ICF, ISI = 13 ms). During vibration relative to squat exercise alone, single-pulse TMS provoked significantly higher TA MEP amplitude (56 Â± 14%, P = 0.003) and total area (71 Â± 19%, P = 0.04), and paired TMS with ISI = 13 ms provoked smaller MEP amplitude (â21 Â± 4%, P = 0.01) but not in SOL. Paired-pulse TMS with ISI = 3 ms elicited significantly lower MEP amplitude (TA, â19 Â± 4%, P = 0.009; and SOL, â13 Â± 4%, P = 0.03) and total area (SOL, â17 Â± 6%, P = 0.02) during vibration relative to squat exercise alone in both muscles. Tibialis anterior MEP facilitation in response to single-pulse TMS suggests that WBV increased corticospinal pathway excitability. Increased TA and SOL SICI and decreased TA ICF in response to paired-pulse TMS during WBV indicate vibration-induced alteration of the intracortical processes as well.
The present study investigated whether differences between adults and children in mechanical power during single-joint knee extension tasks and the complex multijoint task of jumping could be explained by differences in the quadriceps femoris muscle volume. Peak power was calculated during squat jumps, from the integral of the vertical force measured by a force plate, and during concentric knee extensions at 30, 90, 120, 180 and 240 degÂ·s â1 , and muscle volume was measured from magnetic resonance images for 10 men, 10 women, 10 prepubertal boys and 10 prepubertal girls. Peak power during jumping and isokinetic knee extension was significantly higher in men than in women, and in both adult groups compared with children ( P < 0.01), although there were no differences between boys and girls. When power was normalized to muscle volume, the intergroup differences ceased to exist for both tasks. Peak power correlated significantly with quadriceps volume ( P < 0.01), with r 2 values of 0.8, 0.86, 0.81, 0.78 and 0.81 from isokinetic knee extension at angular velocities of 30, 90, 120, 180 and 240 degÂ·s â1 , respectively, and with an r 2 value of 0.9 from squat jumps. These results indicate that the quadriceps femoris muscle volume accounts largely for the increase in power that occurs with maturation in the two genders not only in kinematically constrained knee extensions but also in multijoint tasks. Future studies should examine the role of other factors relating to the generation and transmission of contractile power, such as muscle architecture, tendon stiffness and external mechanical leverage.
Iron accelerates the production of reactive oxygen species (ROS). Excessive levels of ROS are thought to accelerate skeletal muscle fatigue and contribute to the loss of skeletal muscle mass and function with age. Patients with an iron overload disease frequently report symptoms of weakness and fatigue, which is attributed to reduced cardiac function. The contribution of skeletal muscle to these symptoms is unknown. Using a mouse model of iron overload, we determined the extent of iron accumulation in skeletal muscle and the concentrations of the iron storage protein ferritin. The level of oxidative stress, changes in antioxidant enzymes and exercise performance were also assessed. Compared with control mice, the iron overloaded mice had elevated levels of iron in the tibialis anterior muscle and a fourfold increase in ferritin light chain. The oxidative stress product malondialdehyde was increased in the iron group compared with the control group, as was the antioxidant enzyme activity of glutathione reductase and glutathione peroxidase. The iron group performed less work on an endurance test and produced less force in a strength test. Body weight and skeletal muscle weight were lower in the iron group following the intervention. Iron loading reduced the weight of the fast-twitch extensor digitorum longus muscle more than the slow-twitch soleus muscle. In summary, iron accumulation in skeletal muscle may play a significant role in the reduced exercise capacity seen in iron overload disorders and in ageing, and may play an underlying role in skeletal muscle atrophy.
Increased airway Na + absorption mediated by the amiloride-sensitive epithelial Na + channel (ENaC) is a basic defect in cystic fibrosis (CF) lung disease. Cystic fibrosis is one of the most common lethal hereditary diseases and is caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene. The CFTR acts as a cAMP-dependent Cl â channel and regulator of ENaC, and CFTR dysfunction causes impaired Cl â secretion and increased Na + absorption in the airways of CF patients. Evidence from in vitro studies suggested that increased Na + absorption produces airway surface liquid (ASL) volume depletion and led to the generation of transgenic mice with airway-specific overexpression of ENaC to elucidate the role of this mechanism in the in vivo pathogenesis of lung disease. Studies of the pulmonary phenotype of Î²ENaC-overexpressing mice demonstrated that increased airway Na + absorption caused ASL depletion and reduced mucus transport, producing a CF-like lung disease with airway mucus plugging, chronic airway inflammation and pulmonary mortality. Further, recent pharmacological studies demonstrated that preventive, but not late, inhibition of increased airway Na + absorption with the ENaC blocker amiloride reduced morbidity and mortality in this murine model of CF lung disease. These results support a critical role of ENaC in the in vivo pathogenesis of CF lung disease and suggest that amiloride may be an effective preventive therapy for CF patients.
Sympathetic outflow is increased in hypertension. The aim of the present study was to investigate whether the cardiac sympathetic afferent reflex (CSAR) is enhanced in two-kidney one-clip (2K1C) renovascular hypertensive rats, and whether the enhanced CSAR contributes, in part, to the increased sympathetic outflow. Furthermore, the role of central angiotensin II type 1 (AT 1 ) receptors in mediating the CSAR was determined. Under urethane and Î±-chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic denervated and cervical vagotomized rats. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. Compared with sham-operated rats, the CSAR, baseline RSNA and plasma noradrenaline level were significantly enhanced in 2K1C rats. Intrapericardial administration of resiniferatoxin, which abolishes the CSAR because of the desensitization of transient receptor potential vanilloid 1-containing cardiac afferent fibres, decreased the RSNA and MAP. The enhanced CSAR in 2K1C rats was normalized by intracerebroventricular administration of the AT 1 receptor antagonist losartan. Intracerebroventricular administration of angiotensin II further potentiated the enhanced CSAR in 2K1C rats, a response which was abolished by pretreatment with losartan. These results indicate that the CSAR is enhanced in 2K1C rats and the enhanced CSAR contributes, in part, to the sympathetic activation and hypertension. Central AT 1 receptors are involved in the enhanced CSAR in 2K1C rats.
We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (â¼9% in WKY and SHR) and MAP reductions (â8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (â13%) and arteriolar wall/lumen ratio (â35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.