Differential contribution of aortic and carotid sinus baroreflexes to control of heart rate and renal sympathetic nerve activity.

We examined the roles of aortic and carotid sinus baroreceptors in control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in 17 decerebrate rats. The baroreflex curves between the changes in mean arterial blood pressure (MAP) and HR or RSNA in response to intravenous injection of phenylephrine (10-20 µg/kg) or nitroprusside (10 µg/kg) were identified before and following sequential denervation of all four baroafferent nerves. The slope of the MAP-HR curve in the pressor range was decreased (P < 0.05) to 31 ± 7% of the control following denervation of bilateral aortic nerves, whereas it remained substantial (72 ± 10%) following denervation of bilateral carotid sinus nerves. The slope for HR became negligible following complete denervation of all four baroafferent nerves. In contrast, the slope of the MAP-RSNA curve decreased as the sequential baroafferent denervation progressed, irrespective of the denervation order, and it remained well as long as any single baroafferent nerve was intact. The similar influences of sequential baroafferent denervation on the responses of HR and RSNA were observed in the depressor range. Thus, it is likely that aortic and carotid sinus baroreceptors play differential roles in control of HR but they contribute similarly to control of RSNA.

NADPH oxidase contributes to the left ventricular dysfunction induced by sinoaortic denervation in rats.

The aim of this work was to investigate the role nicotinamide adenine dinucleotide phosphate (NADPH) oxidase on left ventricular dysfunction of rats submitted to sinoaortic denervation (SAD). Experiment 1: 8 weeks after SAD of rats, NADPH oxidase in left ventricles was assayed by Western blotting analysis. Experiment 2: Rats were subjected to SAD and received treatment with apocynin (an NADPH oxidase inhibitor, 30 mg/kg/day, intragastric administration) for 8 weeks; 8 weeks after SAD, Nox2 and Nox4 expressions and Rac1 activity of left ventricles were higher in SAD rats than those in sham-operated rats. Although treatment of SAD rats with apocynin did not affect blood pressure, blood pressure variability (BPV), and baroreflex function, it significantly attenuated left ventricular hypertrophy marked by reduced expression of atrial natriuretic factor and ß-myosin heavy chain. Treatment of SAD rats with apocynin abated oxidative stress marked by reduced malondialdehyde formation and suppressed nuclear factor-kappa B (NFκB) activation; inflammation marked by reduced monocyte chemoattractant protein-1 expression and myeloperoxidase activity; attenuated endoplasmic reticulum stress marked by reduced expression of CCAAT-enhancer-binding protein homologous protein, chaperone-glucose-regulated protein 78, and X-box protein 1; and alleviated cardiac fibrosis marked by reduced mRNA levels of collagens I and III and transforming growth factor beta. In conclusion, exaggerated BPV induces chronic myocardial oxidative stress and thereby aggravates cardiac remodeling in rats. These data suggest a potential role of NADPH oxidases in the pathogenesis of cardiac dysfunction induced by exaggerated BPV.

Cardiac impairment evaluated by transesophageal echocardiography and invasive measurements in rats undergoing sinoaortic denervation.

BACKGROUND: Sympathetic hyperactivity may be related to left ventricular (LV) dysfunction and baro- and chemoreflex impairment in hypertension. However, cardiac function, regarding the association of hypertension and baroreflex dysfunction, has not been previously evaluated by transesophageal echocardiography (TEE) using intracardiac echocardiographic catheter. METHODS AND RESULTS: We evaluated exercise tests, baroreflex sensitivity and cardiovascular autonomic control, cardiac function, and biventricular invasive pressures in rats 10 weeks after sinoaortic denervation (SAD). The rats (n = 32) were divided into 4 groups: 16 Wistar (W) with (n = 8) or without SAD (n = 8) and 16 spontaneously hypertensive rats (SHR) with (n = 8) or without SAD (SHRSAD) (n = 8). Blood pressure (BP) and heart rate (HR) did not change between the groups with or without SAD; however, compared to W, SHR groups had higher BP levels and BP variability was increased. Exercise testing showed that SHR had better functional capacity compared to SAD and SHRSAD. Echocardiography showed left ventricular (LV) concentric hypertrophy; segmental systolic and diastolic biventricular dysfunction; indirect signals of pulmonary arterial hypertension, mostly evident in SHRSAD. The end-diastolic right ventricular (RV) pressure increased in all groups compared to W, and the end-diastolic LV pressure increased in SHR and SHRSAD groups compared to W, and in SHRSAD compared to SAD. CONCLUSIONS: Our results suggest that baroreflex dysfunction impairs cardiac function, and increases pulmonary artery pressure, supporting a role for baroreflex dysfunction in the pathogenesis of hypertensive cardiac disease. Moreover, TEE is a useful and feasible noninvasive technique that allows the assessment of cardiac function, particularly RV indices in this model of cardiac disease.

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

Ablation of ventricular arrhythmias arising near the anterior epicardial veins from the left sinus of Valsalva region: ECG features, anatomic distance, and outcome.

BACKGROUND: Left ventricular outflow tract tachycardia/premature depolarizations (VT/VPDs) arising near the anterior epicardial veins may be difficult to eliminate through the coronary venous system. OBJECTIVE: To describe the characteristics of an alternative successful ablation strategy targeting the left sinus of Valsalva (LSV) and/or the adjacent left ventricular (LV) endocardium. METHODS: Of 276 patients undergoing mapping/ablation for outflow tract VT/VPDs, 16 consecutive patients (8 men; mean age 52 ± 17 years) had an ablation attempt from the LSV and/or the adjacent LV endocardium for VT/VPDs mapped marginally closer to the distal great cardiac vein (GCV) or anterior interventricular vein (AIV). RESULTS: Successful ablation was achieved in 9 of the 16 patients (56%) targeting the LSV (5 patients), adjacent LV endocardium (2 patients), or both (2 patients). The R-wave amplitude ratio in lead III/II and the Q-wave amplitude ratio in aVL/aVR were smaller in the successful group (1.05 ± 0.13 vs 1.34 ± 0.37 and 1.24 ± 0.42 vs 2.15 ± 1.05, respectively; P = .043 for both). The anatomical distance from the earliest GCV/AIV site to the closest point in the LSV region was shorter for the successful group (11.0 ± 6.5 mm vs 20.4 ± 12.1 mm; P = .048). A Q-wave ratio of <1.45 in aVL/aVR and an anatomical distance of <13.5 mm had sensitivity and specificity of 89%, 75% and 78%, 64%, respectively, for the identification of successful ablation. CONCLUSIONS: VT/VPDs originating near the GCV/AIV can be ablated from the LSV/adjacent LV endocardium. A Q-wave ratio of <1.45 in aVL/aVR and a close anatomical distance of <13.5 mm help identify appropriate candidates.

Dual tachycardias associating double-exit left aortic sinus cusp tachycardia with paroxysmal atrial fibrillation: evidence of a link between both arrhythmias by means of the autonomic nervous system.

INTRODUCTION: Dual tachycardias associating paroxysmal atrial fibrillation (AF) with double-exit left aortic sinus cusp tachycardia (LASCT) are described for the first time in a patient referred for AF ablation. CASE: Both tachycardias were successfully ablated under Carto-Merge guidance. Noteworthy, vagal denervation during AF ablation was responsible for an immediate decrease in LASCT occurrence and inducibility. CONCLUSION: This case highlights the critical role that the autonomic nervous system plays within the cardiac arrhythmia framework.

Baroreceptor denervation prevents sympathoinhibition during angiotensin II-induced hypertension.

Arterial baroreflexes are well established to provide the basis for short-term control of arterial pressure; however, their role in long-term pressure control is more controversial. We proposed that if the sustained decrease in renal sympathetic nerve activity (RSNA) we observed previously in response to angiotensin II-induced hypertension is baroreflex mediated, then the decrease in RSNA in response to angiotensin II would not occur in sinoaortic-denervated (SAD) animals. Arterial pressure and RSNA were recorded continuously via telemetry in sham and SAD rabbits living in their home cages before, during, and after a 7-day infusion of angiotensin II (50 ng . kg(-1) . min(-1)). The arterial pressure responses in the 2 groups of rabbits were not significantly different (82+/-3 mm Hg sham versus 83+/-3 mm Hg SAD before angiotensin II infusion, and 101+/-6 mm Hg sham versus 100+/-4 mm Hg SAD day 6 of angiotensin II). In sham rabbits, there was a significant sustained decrease in RSNA (53+/-7% of baseline on day 2 and 65+/-7% on day 6 of the angiotensin II). On ceasing the angiotensin II, all variables recovered to baseline. In contrast, RSNA did not change in SAD rabbits with the angiotensin II infusion (RSNA was 98+/-8% of baseline on day 2 and 98+/-8% on day 6 of the angiotensin II infusion). These results support our hypothesis that the reduction in RSNA in response to a pressor dose of angiotensin II is dependent on an intact arterial baroreflex pathway.

Mechanisms of blood pressure variability-induced cardiac hypertrophy and dysfunction in mice with impaired baroreflex.

Enhanced blood pressure variability contributes to left ventricular hypertrophy and end-organ damage, even in the absence of hypertension. We hypothesized that the greater number of high-blood pressure episodes associated with enhanced blood pressure variability causes cardiac hypertrophy and dysfunction by activation of mechanosensitive and autocrine pathways. Normotensive mice were subjected to sinoaortic baroreceptor denervation (SAD) or sham surgery. Twelve weeks later, blood pressure variability was doubled in SAD compared with sham-operated mice. Blood pressure did not differ. Cardiac hypertrophy was reflected in greater heart/body weight ratios, larger myocyte cross-sectional areas, and greater left ventricular collagen deposition. Furthermore, left ventricular atrial and brain natriuretic peptide mRNA expression was greater in SAD than in sham-operated mice. SAD had higher left ventricular end-diastolic pressures and lower myocardial contractility indexes, indicating cardiac dysfunction. Cardiac protein content of phosphorylated p125 focal adhesion kinase (p125 FAK) and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was greater in SAD than in sham-operated mice, indicating activation of mechanosensitive pathways of cardiac hypertrophy. Furthermore, enhanced cardiac renin and transforming growth factor-beta1 (TGFbeta1) protein content indicates activation of autocrine pathways of cardiac hypertrophy. Adrenal tyrosine hydroxylase protein content and the number of renin-positive glomeruli were not different, suggesting that sympathetic activation and the systemic renin-angiotensin system did not contribute to cardiac hypertrophy. In conclusion, more frequent blood pressure rises in subjects with high blood pressure variability activate mechanosensitive and autocrine pathways leading to cardiac hypertrophy and dysfunction even in the absence of hypertension.

Ajustes cardiovasculares provocados pela infusão de solução salina hipertônica em ratos submetidos ao choque hemorrágico: participação de estruturas nervosas / Cardiovascular ajustments induced by infusion of hypertonic saline in rats submitted to hemorrhagic shock: involvement of neural structures

A hiperosmolaridade periférica produzida por infusões endovenosas de soluções de cloreto de sódio hipertônico exerce vários benefícios quando empregada no tratamento do choque hemorrágico em humanos e animais experimentais. Os mecanismos pelos quais estas soluções exercem seus benefícios ainda são motivos de controvérsias, mas provavelmente envolvem expansão de volume plasmático, vasodilatação pré-capilar, venoconstrição, aumento da contratilidade cardíaca e possivelmente uma ação no sistema nervoso central. O objetivo primário deste estudo foi investigar a participação de vias neurais no binômio hipertônica-hemorragia. Com este propósito, nós avaliamos os efeitos de soluções endovenosas de salina hipertônica (NaCl 18 por cento) sobre a pressão arterial média (PAM) e freqüência cardíaca (FC) em ratos anestesiados, submetidos ao choque hemorrágico obtido por sangramento controlado nas seguintes situações: 1. em animais intactos, 2. após vagotomia bilateral, 3. após desnervação sinoaórtica e 4. após desnervação seletiva, aórtica ou carotídea. Foram utilizados ratos Wistar machos (280320g) anestesiados com tiopental sódico i.v. (40 mg/kg) após indução com halotana (2 por cento em 02 100 por cento). Catéteres foram inseridos na veia e artéria femoral esquerda para administração anestésica e medidas de PAM e FC respectivamente. Uma cânula foi inserida na veia jugular direita para sangramento e infusão de soluções salinas. As cânulas para registro da PAM e FC foram conectadas a um transdutor de pressão acoplado a um amplificador e a um sistema de aquisição de análise de dados. Os ratos foram sangrados no intervalo de 30 minutos (2 por cento do peso corpóreo, suficiente para reduzir a pressão arterial média para 60 mmHg) e mantidos hipotensos por mais 30 minutos. A PAM e FC foram analisadas imediatamente antes e após 10, 20, 30, 40, 50, e 60 minutos do início do sangramento. Após este período, os animais recebiam as infusões de salina hipertônica (NaCl 18 por cento) ou salina isotônica (NaCl 0,9 por cento)no volume de 0,18 mU100g de peso corporal, em dose única durante 2 minutos, registrando-se novamente os parâmetros cardiovasculares a cada 10 min até 60 min do término da infusão. Os procedimentos para as desnervações quando pertinentes, eram realizados após a indução do choque hipovolêmico e antes das infusões. Os resultados obtidos demonstraram que: a. em ratos intactos submetidos ao choque hemorrágico, as infusões de NaCl 18 por cento rapidamente…(au)

Inflammation is involved in the organ damage induced by sinoaortic denervation in rats.

OBJECTIVE: The present study was designed to test the hypothesis that inflammation is involved in the end-organ damage (EOD) induced by sinoaortic denervation (SAD) in rats. METHOD: SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. Under anaesthesia, aortic nerves were cut and the sinus region of the carotid artery was stripped and painted with 10% phenol. Pathological evaluation of EOD and the determination of plasma or tissue levels of the factors related to inflammation, including thromboxane B2 (TXB2) interleukin-1 (IL-1), tumour necrosis factor alpha (TNF-alpha) and reactive oxygen species (ROS) were performed at 16 weeks after SAD. Pathological evaluation of EOD included heart weight ratio, myocardial and blood vessel hydroxyproline and collagen volume fraction, glomerular injury score and number of infiltrating inflammatory cells. Indomethacin (20 mg/kg per day, orally) or vitamin E (100 mg/kg per day, orally) was administered for 12 weeks, beginning from 4 weeks after SAD, to observe their effects on SAD-induced EOD. RESULTS: There were significant fibrosis and inflammatory infiltration in the myocardium and blood vessels, represented by higher hydroxyproline and collagen volume fraction, and a large amount of inflammatory cells in the tissues of SAD rats. Heart weight and kidney glomerular injury score were significantly higher in SAD than in sham-operated rats. Plasma TXB2, TNF-alpha, IL-1 and tissue ROS increased significantly after SAD. Indomethacin and vitamin E significantly decreased the contents of some factors related to inflammation in SAD rats. Both drugs also alleviated myocardial and vessel fibrosis, inflammatory infiltration and kidney damage. CONCLUSION: Inflammation is involved in the organ damage induced by SAD in rats.

Apoptosis is involved in the cardiac damage induced by sinoaortic denervation in rats.

1. The arterial baroreflex plays an important role in the maintenance of the stability of blood pressure. Sinoaortic denervation (SAD) produces severe organ damage in rats. The present study was designed to investigate whether apoptosis, which is a ubiquitous physiological mode of cell death distinct from cell mortality induced by injury and necrosis, is involved in SAD-induced cardiac damage. 2. Male Sprague-Dawley rats (10 weeks old) were used. Rats underwent SAD (n = 9) or sham operation (n = 10). Sixteen weeks after operation, the heart tissues were taken for investigations including electron microscopy, immunohistochemistry, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) and reverse transcription-polymerase chain reaction (RT-PCR). 3. Cardiac hypertrophy and fibrosis was found in SAD rats. The number apoptotic cardiomyocytes was increased in SAD rats compared with sham-operated rats. 4. The expression of Bcl-2mRNA and protein (an inhibitory factor of apoptosis) in cardiomyocytes was decreased in SAD rats. In contrast, the expression of Bax, Fas and Fas ligand mRNA and proteins (promoters of apoptosis) in cardiomyocytes was significantly increased in SAD rats. 5. In conclusion, the present study reveals a high level of apoptosis in cardiomyocytes in SAD rats. It is proposed that apoptosis is involved in SAD-induced cardiac damage.

Acute sympathoexcitatory action of angiotensin II in conscious baroreceptor-denervated rats.

Angiotensin II (ANG II) has complex actions on the cardiovascular system. ANG II may act to increase sympathetic vasomotor outflow, but acutely the sympathoexcitatory actions of exogenous ANG II may be opposed by ANG II-induced increases in arterial pressure (AP), evoking baroreceptor-mediated decreases in sympathetic nerve activity (SNA). To examine this hypothesis, the effect of ANG II infusion on lumbar SNA was measured in unanesthetized chronic sinoaortic-denervated rats. Chronic sinoaortic-denervated rats had no reflex heart rate (HR) responses to pharmacologically evoked increases or decreases in AP. Similarly, in these denervated rats, nitroprusside-induced hypotension had no effect on lumbar SNA; however, phenylephrine-induced increases in AP were still associated with transient decreases in SNA. In control rats, infusion of ANG II (100 ng x kg(-1) x min(-1) iv) increased AP and decreased HR and SNA. In contrast, ANG II infusion increased lumbar SNA and HR in sinoaortic-denervated rats. In rats that underwent sinoaortic denervation surgery but still had residual baroreceptor reflex-evoked changes in HR, the effect of ANG II on HR and SNA was variable and correlated to the extent of baroreceptor reflex impairment. The present data suggest that pressor concentrations of ANG II in rats act rapidly to increase lumbar SNA and HR, although baroreceptor reflexes normally mask these effects of ANG II. Furthermore, these studies highlight the importance of fully characterizing sinoaortic-denervated rats used in experiments examining the role of baroreceptor reflexes.

Sympathetic nerve regulation to heating is altered in senescent rats.

Renal and splanchnic sympathetic nerve discharge (SND) responses to increased (38-41 degrees C) internal temperature were determined in anesthetized young (3-6 mo old), mature (12 mo old), and senescent (24 mo old) Fischer 344 (F344) rats. We hypothesized that SND responses would be altered in senescent and mature rats as demonstrated by attenuated sympathoexcitatory responses to heating and by the absence of hyperthermia-induced SND pattern changes. The following observations were made. 1) Renal and splanchnic SND responses were significantly increased during heating in young and mature but not in senescent rats. 2) At 41 degrees C, renal and splanchnic SND responses were higher in young compared with senescent rats, and renal SND was higher in mature than in senescent rats. 3) Heating changed the SND bursting pattern in young, but not in mature or senescent, rats. 4) SND responses to heating did not differ between baroreceptor-innervated (BRI) and sinoaortic-denervated (SAD) senescent rats but were higher in SAD compared with BRI young rats. These results demonstrate an attenuated responsiveness of sympathetic neural circuits to heating in senescent F344 rats.

Microinjection of ANG II into paraventricular nucleus enhances cardiac sympathetic afferent reflex in rats.

The aims of present study were to determine whether angiotensin II (ANG II) in the paraventricular nucleus (PVN) is involved in the central integration of the cardiac sympathetic afferent reflex and whether this effect is mediated by the ANG type 1 (AT(1)) receptor. While the animals were under alpha-chloralose and urethane anesthesia, mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded in sinoaortic-denervated and cervical-vagotomized rats. A cannula was inserted into the left PVN for microinjection of ANG II. The cardiac sympathetic afferent reflex was tested by electrical stimulation (5, 10, 20, and 30 Hz in 10 V and 1 ms) of the afferent cardiac sympathetic nerves or epicardial application of bradykinin (BK) (0.04 and 0.4 microg in 2 microl). Microinjection of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to electrical stimulation. The percent change of RSNA response to 20- and 30-Hz stimulation increased significantly at the highest dose of ANG II (3 nmol). The effects of ANG II were prevented by pretreatment with losartan (50 nmol) into the PVN. Microinjection of ANG II (0.3 nmol) into the PVN significantly enhanced the RSNA responses to epicardial application of BK, which was abolished by pretreatment with losartan (50 nmol) into the PVN. These results suggest that exogenous ANG II in the PVN augments the cardiac sympathetic afferent reflex evoked by both electrical stimulation of cardiac sympathetic afferent nerves and epicardial application of BK. These central effects of ANG II are mediated by AT(1) receptors.

Fos immunoreactivity in the diagonal band and the perinuclear zone of the supraoptic nucleus after hypertension and hypervolaemia in unanaesthetized rats.

We used Fos immunocytochemistry to study the effects of hypertension and hypervolaemia on neurones in the diagonal band of Broca and the perinuclear zone of the supraoptic nucleus, two nuclei that are both involved in the baroreceptor regulation of vasopressin neurones in the supraoptic nucleus. In addition, we used sino-aortic denervation to examine the role of arterial baroreceptors in the response to these haemodynamic changes. Sham-operated and sino-aortic denervated rats were infused with phenylephrine sufficient to increase blood pressure for 2 h. Control rats were infused with the same volume of isontonic saline. Only Sham sino-aortic denervated rats showed reflex bradycardia in response to the increased blood pressure. Volume expansion was produced by infusing the rats with isotonic saline equal to 10% of their body weight for 10 min, which significantly increased central venous pressure. In the diagonal band of Broca and the perinuclear zone, the number of Fos-positive neurones was significantly increased after phenylephrine infusion. Sino-aortic denervation blocked the significant increase in both regions. After volume expansion, a significant increase in Fos staining was observed only in the perinuclear zone of the supraoptic nucleus. This increase was not blocked by sino-aortic denervation. Our results indicate that both the diagonal band of Broca and the perinuclear zone of the supraoptic nucleus are activated by stimulating arterial baroreceptors; however, the perinuclear zone of the supraoptic nucleus is stimulated during volume expansion. Furthermore, the activation of perinuclear zone of the supraoptic nucleus after volume expansion is not dependent on intact arterial baroreceptors.

Sinoaortic denervation abolishes pressure resetting for daily physical activity in rabbits.

It has been speculated that if baroafferent signals are only related to the negative feedback control of arterial pressure (AP), then physical activity would increase the range of AP fluctuation in baroafferent-denervated animals. Mean AP (MAP), heart rate (HR), and cardiac output (CO) were measured for 24 h in free-moving conscious rabbits. On the basis of hydrostatic pressure and electromyogram, MAP data taken during periods of physical activity and rest were selected from the overall 24-h MAP data and then converted into histograms. During physical activity, the mode of MAP histogram increased in intact rabbits and was unchanged in sinoaortic-denervated (SAD) rabbits. Movement increased the mode of total peripheral resistance (TPR) but did not significantly change CO in intact rabbits. Conversely in SAD rabbits, movement slightly decreased TPR and slightly increased CO. These findings indicate that arterial baroafferent signals are required to shift MAP to a higher pressure level by an increase in TPR but not in CO during a moving phase. These results suggest that baroafferent signals may not only minimize the fluctuating range of MAP through negative feedback control but also be involved in actively resetting MAP toward a higher pressure level during daily physical activity.

Frequency response of renal sympathetic nervous activity to aortic depressor nerve stimulation in the anaesthetized rat.

1. The contribution of central baroreceptor reflex pathways to the dynamic regulation of sympathetic nervous activity (SNA) has not been properly examined thus far. The aim of this study was to characterize the transfer function of the central arc of the baroreceptor reflex (from baroreceptor afferent activity to SNA) over a wide range of frequencies. 2. In nine baroreceptor-intact and six sino-aortic baroreceptor-denervated rats anaesthetized with urethane, the renal SNA was recorded while applying sinusoidal stimulation to the aortic depressor nerve at 26 discrete frequencies ranging from 0.03 to 20 Hz. At each modulation frequency, cross-power spectrum analysis using a fast Fourier transform algorithm was performed between the stimulation and renal SNA, which provided the transfer function of the central arc. 3. In both baroreceptor intact and denervated rats, the transfer gain increased by a factor of about three between 0.03 and 1 Hz. At higher frequencies, the gain decreased but remained above the static gain of the system up to 12 Hz. There was a slight phase lead up to 0.4 Hz, then a continuously increasing phase lag. A three-element linear model satisfactorily described the experimental transfer function. The model combined a derivative gain (corner frequency approximately 0.15 Hz), an overdamped second-order low-pass filter (natural frequency approximately 1 Hz) and a fixed time delay (approximately 100 ms). 4. These results indicate that the central arc of the baroreceptor reflex shows derivative properties that are essential for compensating the filtering of fast oscillations of baroreceptor afferent activity and thus for the generation of fast oscillations of renal SNA (e.g. those related to the cardiac cycle).

Baroreceptor and prostanoid control of fetal renal cortical blood flow and plasma renin activity.

Renal function in the fetus is important for maintenance of fetal fluid and electrolyte balance. This study was performed to test the role of prostaglandins and their interaction with arterial baroreceptors and chemoreceptors in the control of renal cortical blood flow during hypotension produced by vena caval obstruction in late-gestation fetal sheep. We studied 18 time-dated, chronically catheterized, fetal sheep (124-136 days gestation). Fetuses were either studied intact (n = 11) or sinoaortic denervated (n = 7), and each fetus was studied twice, with and without pretreatment with indomethacin (0.2 mg kg(-1), i.v.). Each fetus was subjected to hypotension caused by vena caval obstruction for 10 min. Before hypotension, renal cortical blood flow was higher in the vehicle-treated sinoaortic denervated fetuses than in vehicle-treated intact fetuses. The increased renal cortical blood flow observed in the sinoaortic denervated fetuses was counteracted by indomethacin, so that the difference between sinoaortic denervated and intact fetuses was eliminated after indomethacin treatment. Hypotension decreased renal blood flow equally in all groups. Plasma renin activity was increased in response to hypotension in the intact fetuses, but not in the sinoaortic denervated fetuses. Indomethacin treatment, by itself, did not alter plasma renin activity. It is concluded that both arterial baroreceptors and prostanoids influence renal blood flow. Further, renin secretion is influenced by arterial baroreceptors and chemoreceptors and there is no apparent modulatory effect of prostanoids on the baroreflex control of renin secretion.

Dynamic analysis of renal nerve activity responses to baroreceptor denervation in hypertensive rats.

Sinoaortic and cardiac baroreflexes exert important control over renal sympathetic nerve activity. Alterations in these reflex mechanisms contribute to renal sympathoexcitation in hypertension. Nonlinear dynamic analysis was used to examine the chaotic behavior of renal sympathetic nerve activity in normotensive Sprague-Dawley and Wistar-Kyoto rats and spontaneously hypertensive rats before and after complete baroreceptor denervation (sinoaortic and cardiac baroreceptor denervation). The peak interval sequence of synchronized renal sympathetic nerve discharge was extracted and used for analysis. In all rat strains, this yielded systems whose correlation dimensions converged to similar low values over the embedding dimension range of 10 to 15 and whose greatest Lyapunov exponents were positive. In Sprague-Dawley and Wistar-Kyoto rats, compete baroreceptor denervation was associated with decreases in the correlation dimensions (Sprague-DAWLEY: 2.42+/-0.04 to 2.16+/-0.04; Wistar-KYOTO: 2.44+/-0.04 to 2.34+/-0.04) and in the greatest Lyapunov exponents (Sprague-DAWLEY: 0.199+/-0.004 to 0.130+/-0.015; Wistar-KYOTO: 0.196+/-0.002 to 0.136+/-0.010). Spontaneously hypertensive rats had a similar correlation dimension, which was unaffected by complete baroreceptor denervation (2.42+/-0.02 versus 2.42+/-0.03), and a lower value for the greatest Lyapunov exponent, which decreased to a lesser extent after complete baroreceptor denervation (0.183+/-0.006 versus 0.158+/-0.006). These results indicate that removal of sinoaortic and cardiac baroreceptor regulation of renal sympathetic nerve activity is associated with a greater decrease in the chaotic behavior of renal sympathetic nerve activity in normotensive compared with hypertensive rats. This suggests that the central neural mechanisms that regulate renal sympathetic nerve activity in response to alterations in cardiovascular reflex inputs are different in spontaneously hypertensive rats from those in Sprague-Dawley and Wistar-Kyoto rats.