Reflex Control Of Heart Rate Research Articles

The Effect of Physical Resistance Training on Baroreflex Sensitivity of Hypertensive Rats.

Background:Baroreceptors act as regulators of blood pressure (BP); however, its sensitivity is impaired in hypertensive patients. Among the recommendations for BP reduction, exercise training has become an important adjuvant therapy in this population. However, there are many doubts about the effects of resistance exercise training in this population.Objective:To evaluate the effect of resistance exercise training on BP and baroreceptor sensitivity in spontaneously hypertensive rats (SHR).Method:Rats SHR (n = 16) and Wistar (n = 16) at 8 weeks of age, at the beginning of the experiment, were randomly divided into 4 groups: sedentary control (CS, n = 8); trained control (CT, n = 8); sedentary SHR (HS, n = 8) and trained SHR (HT, n = 8). Resistance exercise training was performed in a stairmaster-type equipment (1.1 × 0.18 m, 2 cm between the steps, 80° incline) with weights attached to their tails, (5 days/week, 8 weeks). Baroreceptor reflex control of heart rate (HR) was tested by loading/unloading of baroreceptors with phenylephrine and sodium nitroprusside.Results:Resistance exercise training increased the soleus muscle mass in SHR when compared to HS (HS 0.027 ± 0.002 g/mm and HT 0.056 ± 0.003 g/mm). Resistance exercise training did not alter BP. On the other hand, in relation to baroreflex sensitivity, bradycardic response was improved in the TH group when compared to HS (HS -1.3 ± 0.1 bpm/mmHg and HT -2.6 ± 0.2 bpm/mmHg) although tachycardia response was not altered by resistance exercise (CS -3.3 ± 0.2 bpm/mmHg, CT -3.3 ± 0.1 bpm/mmHg, HS -1.47 ± 0.06 bpm/mmHg and HT -1.6 ± 0.1 bpm/mmHg).Conclusion:Resistance exercise training was able to promote improvements on baroreflex sensitivity of SHR rats, through the improvement of bradycardic response, despite not having reduced BP.

Temporal Development of Autonomic Dysfunction in Heart Failure: Effects of Age in an Ovine Rapid-pacing Model.

Heart failure (HF) is predominantly a disease of older adults and characterized by extensive sympatho-vagal imbalance leading to impaired reflex control of heart rate (HR). However, whether aging influences the development or extent of the autonomic imbalance in HF remains unclear. To address this, we used an ovine model of aging with tachypacing-induced HF to determine whether aging affects the chronotropic and inotropic responses to autonomic stimulation and reduction in heart rate variability (HRV) in HF. We find that aging is associated with increased cardiac dimensions and reduced contractility before the onset of tachypacing, and these differences persist in HF. Additionally, the chronotropic response to β-adrenergic stimulation was markedly attenuated in HF, and this occurred more rapidly in aged animals. By measuring HR during sequential autonomic blockade, our data are consistent with a reduced parasympathetic control of resting HR in aging, with young HF animals having an attenuated sympathetic influence on HR. Time-domain analyses of HR show a reduction in HRV in both young and aged failing animals, although HRV is lowest in aged HF. In conclusion, aging is associated with altered autonomic control and β-adrenergic responsiveness of HR, and these are exacerbated with the development of HF.

Baroreceptor reflex control of heart rate in angiotensin type 1A receptor knockout mice

The baroreceptor reflex dampens the short-term fluctuations in blood pressure by feedback modulation of heart rate (HR) and vascular resistance. Impairment of this reflex has been observed in hypertension and heart failure. Angiotensin II, a blood borne hormone, acts via its type 1A receptor to attenuate the baroreceptor reflex and this reflex is reported to be dramatically altered in angiotensin type 1A receptor knockout mice. This study sought to further investigate changes in the arterial and cardiopulmonary baroreceptor reflex control of HR in angiotensin II type 1A receptor knocked out mice. In artificially ventilated, isoflurane anesthetized mice, the arterial and cardiopulmonary baroreceptor reflexes were activated via injection or slow infusions, respectively, of phenylephrine and sodium nitroprusside through the jugular vein. We observed no impairment of either the arterial or cardiopulmonary baroreceptor reflex control of HR in angiotensin type 1A receptor knockout mice.

Resetting the baroreflex during snoring: Role of resistive loading and intra-thoracic pressure

Baroreflex sensitivity (BRS) is reduced during snoring in humans and animal models. We utilised our rabbit model to examine the contribution of increased upper airway resistance to baroreflex resetting during snoring, by comparing BRS and baroreflex operating point (OP) values during IS to those obtained during tracheostomised breathing through an external resistive load (RL) titrated to match IS levels of peak inspiratory pleural pressure (Ppl). During both IS and RL, BRS decreased by 45% and 49%. There was a linear relationship between the change in Ppl and the decrease in BRS, which was similar for IS and RL. During both RL and IS, there was a shift in OP driven by ∼16% increase in HR and no change in arterial pressure. Snoring related depression of BRS is likely mediated via a HR driven change in OP, which itself may be the outcome of negative intra-thoracic pressure mediated effects on right atrial wall stretch reflex control of heart rate.

New insights into the effects of age and sex on arterial baroreflex function at rest and during dynamic exercise in humans

The arterial baroreflex (ABR) performs an important role in regulating blood pressure (BP) both at rest and during exercise, by carefully orchestrating autonomic neural activity to the heart and blood vessels. Reduced ABR sensitivity (i.e., gain) has been associated with increased cardiovascular risk, cardiac electrical instability and orthostatic intolerance, while 'normal' ABR function during exercise is important for ensuring an appropriate cardiovascular response is elicited. Previous studies examining the influence of age and sex on resting ABR function in humans have primarily used pharmacological methods (e.g., modified Oxford technique) to change BP and alter baroreceptor input. With this approach only reflex control of heart rate and sympathetic nerve activity may be evaluated, and as such the influence of age and sex on ABR control of BP per se remains incompletely understood. Furthermore, the majority of previous studies examining ABR function during exercise have principally assessed young men. Whether these findings can be extrapolated to young women or older men and women remains unclear. Recently the potential for age and sex to modulate the integrative neural control of the cardiovascular system is becoming appreciated. This review article will provide a detailed update of such recent advances into our understanding of the effects of age and sex on ABR control of BP both at rest and during dynamic exercise in humans.

Role of ionotropic GABA, glutamate and glycine receptors in the tonic and reflex control of cardiac vagal outflow in the rat

BackgroundCardiac vagal preganglionic neurons (CVPN) are responsible for the tonic, reflex and respiratory modulation of heart rate (HR). Although CVPN receive GABAergic and glutamatergic inputs, likely involved in respiratory and reflex modulation of HR respectively, little else is known regarding the functions controlled by ionotropic inputs. Activation of g-protein coupled receptors (GPCR) alters these inputs, but the functional consequence is largely unknown. The present study aimed to delineate how ionotropic GABAergic, glycinergic and glutamatergic inputs contribute to the tonic and reflex control of HR and in particular determine which receptor subtypes were involved. Furthermore, we wished to establish how activation of the 5-HT1A GPCR affects tonic and reflex control of HR and what ionotropic interactions this might involve.ResultsMicroinjection of the GABAA antagonist picrotoxin into CVPN decreased HR but did not affect baroreflex bradycardia. The glycine antagonist strychnine did not alter HR or baroreflex bradycardia. Combined microinjection of the NMDA antagonist, MK801, and AMPA antagonist, CNQX, into CVPN evoked a small bradycardia and abolished baroreflex bradycardia. MK801 attenuated whereas CNQX abolished baroreceptor bradycardia. Control intravenous injections of the 5-HT1A agonist 8-OH-DPAT evoked a small bradycardia and potentiated baroreflex bradycardia. These effects were still observed following microinjection of picrotoxin but not strychnine into CVPN.ConclusionsWe conclude that activation of GABAA receptors set the level of HR whereas AMPA to a greater extent than NMDA receptors elicit baroreflex changes in HR. Furthermore, activation of 5-HT1A receptors evokes bradycardia and enhances baroreflex changes in HR due to interactions with glycinergic neurons involving strychnine receptors. This study provides reference for future studies investigating how diseases alter neurochemical inputs to CVPN.

Modulation of Baroreflex Sensitivity by Endogenous Angiotensins in Lamb Solitary Tract Nucleus

We and others find that within the nucleus of the solitary tract (NTS) of the rat endogenous Ang II attenuates while Ang‐(1–7) facilitates the baroreflex sensitivity (BRS) in the control of heart rate. It is not known whether this same relationship exists in the sheep NTS. Therefore, we performed microinjection studies in 6 wk old sheep (n = 5) under chloralose‐urethane anesthesia (35/750 mg/kg) which maintains both increases and decreases in BRS for heart rate control. To assess the effects of blockade of either the AT1 or Ang‐(1–7) (AT7) receptors, we tested BRS before and after bilateral NTS injection of the AT1 antagonist candesartan (CV, 200 pmol/200 nl at 4 injection sites) and retested the reflex again after the AT7 antagonist D‐Ala7‐Ang‐(1–7) (D‐Ala, 10 pmol/200 nl at 4 injection sites). BRS was tested using various doses of phenylephrine to determine the slope of the relationship between changes in mean arterial pressure (MAP) and pulse interval as ms/mm Hg. Resting BRS was 0.3 ± 0.2 ms/mm Hg and MAP was 81 ± 7 mm Hg. NTS injection of CV increased BRS to a new baseline of 1.0 ± 0.2 ms/mm Hg, (p<0.05). From this elevated level D‐Ala significantly reduced BRS back to baseline. There was no effect of either agent on MAP. These data suggest that baseline baroreceptor reflex control of heart rate in lambs is regulated by Ang II and Ang‐(1–7) in the NTS in an opposite manner. Support: HD‐047584, HD‐017644, HL‐51952.

Of founder populations, long QT syndrome, and destiny

Founder populations, characterized by a single ancestor affected by long QT syndrome (LQTS) and by a large number of individuals and families who all are related to the ancestor and thereby carry the same disease-causing mutation, represent the ideal human model for studying the role of "modifier genes" in LQTS. This article reviews some of the fundamental concepts related to founder populations and provides the necessary historical background to understand why so many can be found in South Africa. The focus then moves to a specific LQT1 founder population, carrier of the A341V mutation, that has been studied extensively during the last 10 years and has provided a significant amount of previously unforeseen information. These novel findings range from an unusually high clinical severity not explained by the electrophysiologic characteristics of the mutation, to the importance of tonic and reflex control of heart rate for risk stratification, to the identification of the first modifier genes for clinical severity of LQTS.

Aortic baroreceptor function and depressed baroreflex sensitivity following myocardial infarction

Depressed sinoaortic baroreflex control of heart rate following myocardial infarction (MI) is associated with increased morbidity and mortality. The etiology of this autonomic disturbance is unknown but could potentially occur at several levels of the reflex arc. The purpose of this study was to assess whether depressed baroreflex sensitivity (BRS) post-MI is associated with aortic baroreceptor dysfunction.BRS was measured before and 4–8 weeks after anterior MI in 17 chronically-instrumented, trained, conscious dogs. BRS (ms/mm Hg) was defined as the slope of the relationship between changes in systolic blood pressure (SBP) and heart period in response to a bolus dose of phenylephrine (PE). After the effects of MI on BRS were determined, the animals were anesthetized and the aortic depressor nerves (ADN) were isolated from the cervical vagi. Aortic baroreceptor function was measured by direct recording of ADN activity during gradual elevation of SBP induced by PE infusion.BRS was depressed following MI in 7 of these dogs and preserved in the remaining 10. Aortic baroreceptor sensitivity (ABS) defined as the slope of the relationship between changes in ADN activity and SBP was not significantly different between the dogs with depressed BRS compared to the dogs with preserved BRS post-MI.In conclusion, the response of the aortic baroreceptors to an increase in SBP is similar in dogs with and without depressed BRS post-MI. Based on these data, we conclude that depressed reflex control of heart rate following MI is not related to dysfunction of the afferent limb of the sinoaortic baroreflex.

The Effect Of Atropine On Cerebral Perfusion During Systemic Hypotension

PURPOSE: The aim of this study was to seek the importance of reflex control of heart rate (HR) in maintaining cerebral perfusion during systemic hypotension. METHODS: Eight healthy subjects (28.4±1.9 yr) gave the written consent to participate in the study that was approved by IRB at UNTHSC. Systemic hypotension was elicited by cuff deflation (CD) following 3-min bilateral supra-systolic occlusion at rest and during lower-body negative pressure (LBNP). RESULTS: Atropine increased baseline HR from 63±2 to 103±3 bpm. However, neither middle cerebral arterial blood flow velocity (VMCA, Doppler) nor mean arterial pressure (MAP, Tonometry) was significantly altered by atropine (before vs after: 66.3±4.0 vs 70.1±4.8 cm/s and 84±4 vs 87±4 mmHg). Though CD elicited hypotension was greater after atropine, the decreases in VMCA were not different (see Table 1). Nonetheless, MAP recovery time following CD was not different before and after atropine despite significant diminution of the tachycardiac response. VMCA recovery time had a trend (P = 0.10) to be longer after atropine.Table 1: Response to cuff deflation after 3-min supra-systolic occlusionCONCLUSION: MAP recovery remained fully compensated after atropine, whereas VMCA recovery was partially dependent on HR reflex.

Long-term treatment with supraphysiological doses of nandrolone decanoate reduces the sensitivity of Bezold–Jarisch reflex control of heart rate and blood pressure

We investigated the influence of long-term treatment with supraphysiological doses of an anabolic-androgenic steroid on the Bezold–Jarisch reflex (BJR) control of heart rate (HR) and diastolic arterial pressure (DAP), and whether this treatment induced cardiac hypertrophy. Male rats were treated with nandrolone decanoate (ND) (10 mg kg −1 body weight for 8 weeks; DECA) or vehicle (control animals; CON). After 8 weeks of treatment, the BJR was evaluated by bradycardia and hypotension responses that were elicited by serotonin administration (2–32 μg kg −1). Mean arterial pressure (MAP) was assessed and cardiac hypertrophy was determined by the ratio of the left and right ventricle weight/body weight (LVW/BW and RVW/BW, respectively) and by histological analysis. Total body protein (TBP) content was also evaluated. Nandrolone decanoate treatment increased MAP (CON = 99 ± 1 mmHg; DECA = 109 ± 2 mmHg; p < 0.01) but did not change the mean basal HR (CON = 356 ± 13 bpm; DECA = 367 ± 11 bpm). The treatment also induced LV and RV hypertrophy (LVW/BW: CON = 1.86 ± 0.04 mg g −1, DECA = 2.17 ± 0.04 mg g −1, p < 0.01; RVW/BW: CON = 0.42 ± 0.02 mg g −1, DECA = 0.53 ± 0.03 mg g −1, p < 0.05) and reduced the number of myocyte nuclei/high-power field (CON = 23.0 ± 2; DECA = 9.4 ± 1.0; p < 0.01). ND treatment blunted the HR and DAP decreases induced by serotonin. ND determines an increase in the TBP content in DECA group (35 ± 3%; p < 0.01) compared with control animals (18 ± 1%). We conclude that 8 weeks of ND treatment induces anabolic effect, cardiac hypertrophy and an elevation of MAP. This treatment also reduces the sensitivity of the BJR control of bradycardia and blood pressure, possibly due to cardiac hypertrophy. The blunted BJR response could contribute to the MAP elevation in DECA animals.

Estimulación cerebral profunda: 12 años de experiencia y 250 pacientes intervenidos con un seguimiento de más de un año

Deep brain stimulation (DBS) is a widely accepted clinical technique. The main motor symptoms are significantly reduced. The success of the technique depends on the experience of the neurosurgeon, neurologist and neurophysiologist who carry it out. The presentation of extensive series is needed to confirm and further currently held knowledge. To demonstrate the clinical benefits of a long series of patients treated by a single group with a minimum follow-up of one year and to report new neurophysiological data. The study examined a total of 250 patients with different diagnoses: most of them with Parkinson's disease, tremor and dystonia. The nuclei that were chosen were located by magnetic resonance imaging, computerised axial tomography and neurophysiological registers. Neurophysiological exclusion criteria, such as reflex control of heart rate, sympathetic skin response and auditory startle reflex, are employed in order to exclude patients with Parkinson-plus. The motor sub-scale (part III) of the Unified Parkinson's Disease Rating Scale improves by 64% in the off-medication status with sub-thalamic stimulation at one year after surgery. One year after DBS, patients with dystonia show a significant decrease on the Burke-Fahn-Marsden dystonia scale. The improvement on the scales continues, with a mean descent of 65% in the second year after surgery. DBS is a suitable technique for the treatment of movement disorders. The neuronal activity of the sub-thalamus and the internal globus pallidus presents its own characteristics that reflect the motor symptoms of the patients. Surface electromyography proves to be useful for quantifying the patients' improvement.

Restorative Effect of Atrial Natriuretic Peptide or Chronic Neutral Endopeptidase Inhibition on Blunted Cardiopulmonary Vagal Reflexes in Aged Rats

Arterial baroreflex function diminishes with age, but whether cardiopulmonary vagal reflexes are similarly altered with physiological aging has not been fully elucidated. In this study, predominantly cardiac high pressure mechanoreceptor-activated (ramp baroreflex) and cardiopulmonary chemoreceptor-activated (von Bezold-Jarisch reflex) vagal reflexes in conscious, instrumented rats were impaired by 30% to 40% (P<0.05) in 24-month-old (n=12) compared with 6-month-old rats (n=12). To determine whether this is a restorable deficit, the influence of atrial natriuretic peptide (ANP), either by infusion or blockade of its breakdown, was studied. ANP infusion was previously shown to enhance Bezold-Jarisch reflex and ramp baroreflex bradycardia in young adult rats. The present study confirmed that vagal reflex augmentation by ANP (50 pmol/kg per minute) also occurs in old rats (increased by 60+/-18% (Bezold-Jarisch reflex) and 91+/-15% (ramp baroreflex; P<0.05). Direct vagal stimulation in anesthetized animals showed that the target for ANP was not the cardiac vagus itself in old rats (n=7), although in young rats only, we confirmed the published finding that ANP enhances vagal bradycardia (by 58+/-14%, n=7). Neutral endopeptidase 24.11 degrades ANP and several other peptides. The neutral endopeptidase inhibitor candoxatrilat (5 mg/kg per day IV for 7 to 9 days) restored vagal reflex bradycardia in old rats (n=6) to levels similar to those in young neutral endopeptidase inhibitor-treated rats (n=6). Impaired cardiopulmonary vagal reflex control of heart rate is thus a feature of normal aging, and this deficit may be ameliorated by either ANP infusion or chronic neutral endopeptidase inhibition.

Reflex control of sympathetic outflow and depressed baroreflex sensitivity following myocardial infarction

Reflex control of heart rate is frequently impaired following myocardial infarction. This is referred to as depressed baroreflex sensitivity. The aim of these experiments was to assess the function of other autonomic reflexes in dogs with depressed baroreflex sensitivity. Comparisons were made to dogs in whom baroreflex sensitivity was preserved or unchanged after myocardial infarction. Under chloralose–barbiturate anesthesia, reflex control of sympathetic outflow by the sinoaortic baroreceptors was determined by measurement of changes in systolic arterial pressure and efferent renal sympathetic nerve activity during infusion of phenylephrine. Following sinoaortic denervation, reflex control of sympathetic outflow by cardiac receptors with vagal afferent fibers was determined by measurement of changes in pulmonary capillary wedge pressure and renal nerve activity during blood volume expansion.Reflex decreases in renal nerve activity in response to increases in arterial pressure were similar in the two groups of dogs. In contrast, elevation of pulmonary capillary wedge pressure elicited significantly greater reflex decreases in renal nerve activity in dogs with depressed baroreflex sensitivity following myocardial infarction compared to dogs with preserved baroreflex sensitivity. Hemodynamic parameters and infarct sizes were similar in each group.In conclusion, activation of cardiac receptors with vagal afferent fibers elicited greater reflex inhibition of sympathetic outflow in dogs with depressed baroreflex sensitivity following myocardial infarction. These data suggest that these receptors are “sensitized”. These results provide additional support for the hypothesis that depressed reflex control of heart rate following myocardial infarction is related to augmented afferent input from the left ventricle.

Angiotensin-(1-7) and Baroreflex Function in Nucleus Tractus Solitarii of (mRen2)27 Transgenic Rats

Endogenous angiotensin (Ang)-(1-7) enhances, while Ang II attenuates, baroreceptor sensitivity (BRS) for reflex control of heart rate (HR) in Sprague-Dawley (SD) rats. In (mRen2)27 renin transgenic rats [(mRen2)], there is overexpression of the mouse Ren2 gene in brain, leading to elevated Ang II and reduced Ang-(1-7) in brain medullary, and associated with hypertension and impaired BRS. We therefore tested the contribution of endogenous Ang-(1-7) to BRS for control of HR and responses to cardiac vagal chemosensitive afferent fiber activation (CVA) with phenylbiguanide (PBG) in anesthetized SD and (mRen2) 27 rats before and after bilateral nucleus of the solitary tract (nTS) injection of the Ang-(1-7) receptor antagonist (D-Ala7)-Ang-(1-7). (mRen2) 27 rats exhibited a approximately 50% impairment in BRS as compared with SD (P < 0.05). (D-Ala7)-Ang-(1-7) attenuated BRS by approximately 50% in SD rats, but was without effect in (mRen2) 27 rats. (D-Ala7)-Ang-(1-7) did not alter the responses to CVA by PBG (iv bolus) in either strain. There were no differences in the depressor effects of Ang-(1-7) injected into the nTS, nor were levels of mRNA different for angiotensin-converting enzyme, angiotensin-converting enzyme 2, neprilysin, or the mas receptor in medullary tissue from SD versus (mRen2)27 rats. Endogenous Ang-(1-7) does not provide tonic input in the nTS to modulate BRS for control of HR in (mRen2)27 rats, which may contribute to impairment of BRS in these animals.

Baroreceptor reflex modulation by circulating angiotensin II is mediated by AT1receptors in the nucleus tractus solitarius

Circulating ANG II modulates the baroreceptor reflex control of heart rate (HR), at least partly via activation of ANG II type 1 (AT1) receptors on neurons in the area postrema. In this study, we tested the hypothesis that the effects of circulating ANG II on the baroreflex also depend on AT1 receptors within the nucleus tractus solitarius (NTS). In confirmation of previous studies in other species, increases in arterial pressure induced by intravenous infusion of ANG II had little effect on HR in urethane-anesthetized rats, in contrast to the marked bradycardia evoked by equipressor infusion of phenylephrine. In the presence of a continuous background infusion of ANG II, the baroreflex control of HR was shifted to higher levels of HR but had little effect on the baroreflex control of renal sympathetic activity. The modulatory effects of circulating ANG II on the cardiac baroreflex were significantly reduced by microinjection of candesartan, an AT1 receptor antagonist, into the area postrema and virtually abolished by microinjections of candesartan into the medial NTS. After acute ablation of the area postrema, a background infusion of ANG II still caused an upward shift of the cardiac baroreflex curve, which was reversed by subsequent microinjection of candesartan into the medial NTS. The results indicate that AT1 receptors in the medial NTS play a critical role in modulation of the cardiac baroreflex by circulating ANG II via mechanisms that are at least partly independent of AT1 receptors in the area postrema.

Corrigendum

CORRIGENDUMCorrigendumPublished Online:01 Sep 2006https://doi.org/10.1152/ajpheart.00692.2006Original articleMoreSectionsPDF (21 KB)Download PDF ToolsExport citationAdd to favoritesTrack citations ShareShare onFacebookTwitterLinkedInWeChat Volume 288, May 2005Volume 57, May 2005Pages H2422–H2430. Moffitt, Julia A., Angela J. Grippo, and Alan Kim Johnson. Baroreceptor reflex control of heart rate in rats studied by induced and autogenic changes in arterial pressure. Am J Physiol Heart Circ Physiol 288: H2422–H2430, 2005 (doi: 10.1152/ajpheart.00057.2004).In methods, in the section Baroreflex Assessment Protocol, the sampling rate appeared incorrectly. It should read: “Data were acquired at 1,000 samples/s.”This article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated ArticlesBaroreceptor reflex control of heart rate in rats studied by induced and autogenic changes in arterial pressure 01 May 2005American Journal of Physiology-Heart and Circulatory Physiology More from this issue > Volume 291Issue 3September 2006Pages H1488-H1488 Copyright & PermissionsCopyright © 2006 by the American Physiological Societyhttps://doi.org/10.1152/ajpheart.00692.2006History Published online 1 September 2006 Published in print 1 September 2006 Metrics

Impaired Baroreceptor Reflex Function of Older ASrAOGEN Rats

Generation of Ang-(1–7) in the dorsal medulla through pathways catalyzed by neprilysin and ACE2 decreases in Sprague-Dawley (SD) rats as they age. Further, we have shown that reduced tissue Ang-(1–7) in aging rats (~70 weeks) contributes to a 40% reduction in baroreceptor reflex control of heart rate associated with increased systolic blood pressure (SBP). On the other hand, transgenic rats with low brain angiotensinogen (ASrAOGEN) do not exhibit increases in SBP as they age. However, data on age-related changes in baroreflex function of ASrAOGEN rats is lacking. Therefore, we assessed baroreflex control of heart rate in Young (3 – 4 months) and Older (15 – 16 months) conscious male ASrAOGEN rats as the slope of the relationship between phenylephrine-induced increases in blood pressure and decreases in heart rate. The heart rate baroreflex was attenuated in Older rats compared to Young rats (1.6 ± 0.6, n = 8 vs 3.6 ± 1.0 msec/mmHg, n = 4, respectively; p< 0.05). Further, heart rate baroreflex sensitivity of older SD rats [0.7 ± 0.2 msec/mmHg (n = 7)] was significantly less than that of older ASrAOGEN rats. Thus, heart rate baroreflex sensitivity declined with age in ASrAOGEN rats but remained higher than that of older SD rats. Since neprilysin and ACE2 mRNAs and Ang-(1–7) forming activity of these enzymes tends to be reduced in medulla oblongata of older ASrAOGEN and SD rats in comparison to that of younger rats, we suggest that decline in local production of Ang-(1–7) contributes to attenuated baroreflex function of ASrAOGEN and SD rats as they age. Support: HL51952; AHA-MA 021515U

Reference values for the 6-min walk test in healthy subjects 20–50 years old

In 102 healthy Caucasians, 20-50 years old, we investigated the effect of anthropometrics on the 6-min walk test (6MWT), in order to provide reference values for walk distance (6MWD), oxygen saturation (SpO2), pulse rate (PR), respiratory rate (RR), breathlessness perception (VAS) and for the walking distance and body weight product (DW). The mean 6MWD and DW values were 593 +/- 57 and 638+/-44 m (P < 0.01) and 35,030 +/- 5306 and 48,882 +/- 6555 kg m (P < 0.01), respectively for women and for men. While walking, SpO2 remained unaltered and subjects reached 67 +/- 10% of their maximal predicted heart rate and a RR mean value of 19 +/- 4 bpm. VAS ratings were significantly higher in females as compared to males (24 +/- 15 vs. 18 +/- 5 mm, P < 0.05), however, when corrected for PR change while walking, they were not different. The equation by stepwise multiple regression analysis included height, age and gender for the 6MWD and accounted for 42% of the total variance. This study confirms the relevant effect of anthropometrics on walking capacity and suggests that when rating dyspnea, the change in heart rate during walking should be considered.

Baroreceptor reflex control of heart rate in rats studied by induced and autogenic changes in arterial pressure

The function of the arterial baroreflex has traditionally been assessed by measurement of reflex changes in heart rate (HR) or sympathetic nerve activity resulting from experimenter-induced manipulation of arterial blood pressure (the Oxford method, also termed the pharmacological method). However, logistical and flexibility limitations of this technique have promoted the development of new methods for assessing baroreflex function such as the evaluation of changes in spontaneous arterial pressure and HR. Although this new spontaneous method has been validated in dogs and humans, it has not been rigorously tested in rats. In the present study, the method of correlating spontaneous changes in systolic blood pressure and HR was evaluated in resting, normotensive Sprague-Dawley rats. This technique was found to be neither reliable nor valid under the conditions employed in the present protocol. We also tested a variation of the spontaneous method that evaluates particular sequences of data during which arterial pressure and pulse interval are changing in the same direction for at least three consecutive heartbeats (the sequence method). The sequence method did not provide extra reliability or validity over the spontaneous method. We conclude that due to the restricted range of variability obtained by measuring spontaneous blood pressure fluctuations, the spontaneous and sequence techniques do not provide data that are comparable to the traditional method of assessing HR changes triggered by arterial blood pressure increases and decreases induced by vasoactive drugs. However, it is possible that surgical stress obscured the relationship between blood pressure and HR, and therefore additional studies are needed to determine whether the spontaneous and sequence methods can be applied to rats during different behavioral states.