Baroreflex Control Of Heart Rate Research Articles

SOD1 Overexpression Preserves Baroreflex Control of Heart Rate with an Increase of Aortic Depressor Nerve Function

Overproduction of reactive oxygen species (ROS), such as the superoxide radical (O2 ∙−), is associated with diseases which compromise cardiac autonomic function. Overexpression of SOD1 may offer protection against ROS damage to the cardiac autonomic nervous system, but reductions of O2 ∙− may interfere with normal cellular functions. We have selected the C57B6SJL-Tg (SOD1)2 Gur/J mouse as a model to determine whether SOD1 overexpression alters cardiac autonomic function, as measured by baroreflex sensitivity (BRS) and aortic depressor nerve (ADN) recordings, as well as evaluation of baseline heart rate (HR) and mean arterial pressure (MAP). Under isoflurane anesthesia, C57 wild-type and SOD1 mice were catheterized with an arterial pressure transducer and measurements of HR and MAP were taken. After establishing a baseline, hypotension and hypertension were induced by injection of sodium nitroprusside (SNP) and phenylephrine (PE), respectively, and ΔHR versus ΔMAP were recorded as a measure of baroreflex sensitivity (BRS). SNP and PE treatment were administered sequentially after a recovery period to measure arterial baroreceptor activation by recording aortic depressor nerve activity. Our findings show that overexpression of SOD1 in C57B6SJL-Tg (SOD1)2 Gur/J mouse preserved the normal HR, MAP, and BRS but enhanced aortic depressor nerve function.

Abstract P189: Angiotensin II - Endocannabinoid Interactions in the Nucleus of the Solitary Tract are Important for Regulation of Baroreflex Control of Heart Rate

Hypertension resulting from elevated brain angiotensin (Ang) II is associated with impaired functioning of neural reflexes regulating sympathetic and parasympathetic outflow. Restoration of normal baroreflex sensitivity (BRS) for control of heart rate (HR) is achieved in a rat model of Ang II - dependent hypertension [ (mRen2)27 transgenic rats ] by local injection of the cannabinoid CB 1 receptor antagonist rimonabant (SR141716A), a CB 1 receptor antagonist, into the solitary tract nucleus (NTS) of anesthetized rats or by chronic oral rimonabant treatment, which has central and peripheral sites of action. Together with elevated brain dorsal medullary tissue concentrations of 2-arachidonylglycerol present in the (mRen2)27 rats, these findings are consistent with an activated endocannabinoid system contributing to the impaired BRS in these animals. To further explore acute interactions between Ang II - mediated suppression of BRS and the endocannabinoids, Ang II was injected into NTS of anesthetized Sprague-Dawley rats 10 minutes following NTS injection of rimonabant or aCSF (120 nL, bilaterally). In the presence of aCSF, Ang II reduced BRS by ~50% (In msec/mm Hg: 1.14 ± 0.14 before versus 0.53 ± 0.16; n = 7, p < 0.008); this effect was abolished in the presence of rimonabant (In msec/mm Hg: 0.92 ± 0.16 before versus 0.86 ± 0.21; n = 4, p = 0.8). There was no difference in mean arterial pressure or heart rate before or after Ang II treatment in either aCSF or rimonabant groups. Thus, the data support the interpretation that Ang II - mediated attenuation of BRS for control of HR involves release of endocannabinoids. Others report that the pressor actions following acute local injections of Ang II into the hypothalamic paraventricular nucleus are prevented by blockade of CB 1 receptors. We conclude that functional interactions between these two systems occur at multiple brain sites relevant to blood pressure control mechanisms and together the findings support a role for elevated brain endocannabinoids as contributors to the altered reflexes characteristic of Ang II - dependent hypertension. Support: HL-51952, DA-024863 and DA-03690, the Hypertension & Vascular Research Center, Farley[[Unable to Display Character: ‐]]Hudson Foundation

Developmentally regulated effects of severe hemorrhage on cardiovascular homeostasis and the arterial baroreflex control of heart rate.

The purpose of this study was to investigate in developing animals, the cardiovascular responses to severe hemorrhage at which compensatory mechanisms fail and when blood pressure remains decreased after blood loss. Two groups of conscious lambs (Group I: one to two weeks, N = 7; group II: six to seven weeks, N = 7) were studied. Mean arterial pressure, systolic and diastolic pressures, and heart rate were measured for 20 min before (Control, C) and for 60 min after a fixed hemorrhage of 30% of blood volume. The arterial baroreflex control of heart rate was assessed before (C), and at 30 and 60 min intervals after hemorrhage. Mean arterial pressure decreased for up to 60 min after hemorrhage in both groups of lambs. In group I, heart rate decreased from 200 ± 29 (C) to 164 ± 24 beat min−1 at 30 min then increased to 232 ± 45 beat min−1 at 60 min, whereas heart rate remained unaltered in group II. With respect to the arterial baroreflex control of heart rate, by 30 min after hemorrhage in group I, there was a decrease in the heart rate range over which the baroreflex operates (P1) from 192 ± 13 (C) to 102 ± 9 beats min−1; by 60 min after hemorrhage, there was a decrease in minimum heart rate (P4) from 72 ± 10 (C) to 32 ± 25 beats min−1. In group II, P1 decreased to a lesser extent than group I from 134 ± 21 (C) to 82 ± 10 beats min−1 at 30 min; minimum heart rate (P4) decreased from 40 ± 15 (C) to 24 ± 9 and 20 ± 13 beats min−1 at 30 and 60 min, respectively. These results provide the first assessment of the arterial baroreflex control of heart rate following blood loss and new evidence that the cardiovascular responses to severe hemorrhage are developmentally regulated.

Abnormal central control underlies impaired baroreflex control of heart rate and sympathetic nerve activity in female Lewis polycystic kidney rats.

Why baroreflex dysfunction occurs in females with chronic kidney disease is unknown. We therefore aimed to examine whether temporal changes in baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) occur in female Lewis polycystic kidney (LPK) rats and whether this is associated with any changes in afferent, central or efferent processing of the reflex pathway. Using urethane-anaesthetized juvenile and adult LPK and Lewis control rats (n = 40), baroreflex-mediated changes in HR, RSNA and aortic depressor nerve activity (ADNA) were examined. Reflex changes to aortic depressor and vagal efferent nerve stimulation were also determined. In the juvenile LPK rats, except for a slight reduction in the gain of the normalized HR and RSNA baroreflex function curves, no difference in baroreflex control of HR, RSNA or ADNA was observed. Responses to aortic depressor and vagal efferent nerve stimulation were also comparable. In the adult hypertensive LPK rats, the range of both HR (35 ± 8 vs. 78 ± 9 bpm, P ≤ 0.05 LPK vs. Lewis) and RSNA (60 ± 7 vs. 80 ± 3%, P ≤ 0.05 LPK vs. Lewis) was also reduced. This was not associated with any change in the ADNA baroreflex function curves or reflex HR responses to vagal efferent nerve stimulation, but was associated with a reduction in the reflex bradycardic (-21 ± 4 vs. -34 ± 8 bpm, P < 0.01 LPK vs. Lewis) and sympathoinhibitory (-30 ± 8 vs. -54 ± 12%, P < 0.001 LPK vs. Lewis) responses to aortic depressor nerve stimulation. In female LPK rats, baroreflex dysfunction results from impaired central processing of the reflex.

Effect of Bilateral Carotid Body Resection on Cardiac Baroreflex Control of Blood Pressure During Hypoglycemia

Hypoglycemia results in a reduction in cardiac baroreflex sensitivity and a shift in the baroreflex working range to higher heart rates. This effect is mediated, in part, by the carotid chemoreceptors. Therefore, we hypothesized hypoglycemia-mediated changes in baroreflex control of heart rate would be blunted in carotid body-resected patients when compared with healthy controls. Five patients with bilateral carotid body resection for glomus tumors and 10 healthy controls completed a 180-minute hyperinsulinemic, hypoglycemic (≈3.3 mmol/L) clamp. Changes in heart rate, blood pressure, and spontaneous cardiac baroreflex sensitivity were assessed. Baseline baroreflex sensitivity was not different between groups (P>0.05). Hypoglycemia resulted in a reduction in baroreflex sensitivity in both the groups (main effect of time, P<0.01) and responses were lower in resected patients when compared with controls (main effect of group, P<0.05). Hypoglycemia resulted in large reductions in systolic (-17±7 mm Hg) and mean (-14±5 mm Hg) blood pressure in resected patients that were not observed in controls (interaction of group and time, P<0.05). Despite lower blood pressures, increases in heart rate with hypoglycemia were blunted in resected patients (interaction of group and time, P<0.01). Major novel findings from this study demonstrate that intact carotid chemoreceptors are essential for increasing heart rate and maintaining arterial blood pressure during hypoglycemia in humans. These data support a contribution of the carotid chemoreceptors to blood pressure control and highlight the potential widespread effects of carotid body resection in humans.

The Effect of Multiple Sclerosis on Carotid Baroreflex Control of Heart Rate and Blood Pressure

Multiple sclerosis (MS), a progressive neurological disease, can result in impairments in autonomic control of cardiovascular function. We tested the hypothesis that patients with MS (n=5) exhibit a blunted response following baroreflex perturbation compared to sex and age matched healthy controls (CON: n=5). At rest, 5‐sec pulses of neck suction (NS; ‐60 Torr) and neck pressure (NP; +40 Torr) were applied to simulate carotid hypertension and hypotension, respectively. Mean arterial pressure (MAP; finger photoplethysmography) and heart rate (HR) were continuously measured in response to the perturbations. Following NS, responses in MAP (MS: ‐11±5 mmHg, CON: ‐10±3 mmHg; p=0.59) and HR (MS: ‐8±3 BPM, CON: ‐8±4 BPM; p=0.93) were similar between groups. While HR response (MS: 5±5 BPM, CON: 5±4 BPM; p=0.94) following NP was no different, a difference in MAP approached significance (MS: 6±2 mmHg, CON: 8±2 mmHg; p=0.09). These data suggest that patients with MS demonstrate a diminished ability to increase MAP to hypotensive stimuli compared to healthy controls.&#x0D; Supported by NIH R15HL117224 and National MS Society RG4696A

Chronic Intermittent Hypoxia (CIH) Enhances Nucleus Tractus Solitarius (NTS) Barosensitive Neuronal Activity in Response to Arterial Pressure Increase in F344 rats

Previously, we showed that baroreflex control of heart rate (HR) is reduced but aortic baroreceptor afferent function is enhanced in CIH rats. The goal of this study was to determine the effect of CIH on NTS. F344 rats (4 mo) were exposed to either room air (RA; n=10) or CIH (6 minutes cycles of 21% and 10% O2, 12‐h/day, n=11) for 35‐50 days. Following CIH exposure, rats were anaesthetized with Ket/Ace. Single‐unit extracellular recording was made of NTS barosensitive neurons responding to mean arterial pressure (MAP) changes induced by descending aorta occlusion and measured from the carotid artery. The baseline MAP and HR were similar in RA and CIH. Baseline NTS neuronal firing was 5.6±0.9 spikes/s for RA (n=24) and 6.1±1.0 spikes/s for CIH (n=29). Aortic occlusion‐induced ΔMAP was similar: 26.7±1.0 mmHg (RA) and 26.7±0.8 mmHg (CIH). The time from 5% MAP increase (relative to baseline) to MAP peak was comparable (RA: 5.3±0.6 s, CIH: 5.4±0.3 s). The time from response threshold (30% increase relative to baseline) to NTS neuron peak response was shorter in CIH compared to RA (4.1±0.3 s vs 5.5±0.5s, p&lt;0.05). The time between 5% MAP increase and NTS response threshold was not different between RA and CIH neurons (3.1±0.5s, 3.6±0.5s). Data from the neurons that had short response time (蠄3 s) were used to construct logistic sigmoidal curves (n = 16/group). Based on Gainmax, we identified two groups of neurons. CIH neurons increased NTS response Gainmax [6.4±4.4 (RA) vs 10.54±3.5 (CIH) in grp 1 and 31.9±3.7 (RA) vs 55.5±9.3 (CIH) in grp 2, p&lt;0.05] and range [78.9±11.9 (RA) vs 131.7±21.2(CIH) in grp 1 and 211.2±34.8 (RA) vs 471.6±120.1 (CIH) in grp 2, p&lt;0.05], but did not alter MAP50. Our data suggest that CIH increased output of NTS barosensitive neurons in rats.

Effect of Carotid Body Resection on Baroreflex Control of Blood Pressure During Hypoglycemia

BackgroundHypoglycemia results in a reduction in spontaneous cardiac baroreflex sensitivity (scBRS) and a shift in the baroreflex working range to higher heart rates; this effect may be mediated by the carotid chemoreceptors. We hypothesized changes in baroreflex control of heart rate with hypoglycemia would be blunted in carotid body resected patients when compared with healthy controls.MethodsFive patients (3M/2F) with bilateral carotid body resection for glomus tumors and ten healthy controls (7M/3F) completed a 180‐min hyperinsulinemic, hypoglycemic (~3.3 µmol/mL) clamp. Changes in heart rate, blood pressure, and scBRS were assessed.ResultsscBRS was reduced from baseline during hypoglycemia (p&lt;0.01) and was lower in carotid body resected patients when compared with controls (p=0.01). Hypoglycemia‐mediated reductions in systolic and mean blood pressure were significantly greater in patients when compared with controls (p&lt;0.05). Despite lower blood pressures, increases in heart rate with hypoglycemia were blunted in patients (p&lt;0.01).ConclusionReductions in scBRS with hypoglycemia cannot be exclusively attributed to the carotid chemoreceptors; however, the chemoreceptors play a role in resetting the baroreflex working range to higher heart rates during hypoglycemia such that a rise in heart rate is not observed in carotid body resected patients. These data support a contribution of the carotid chemoreceptors to baroreflex control of blood pressure during hypoglycemia and highlight potential widespread effects of carotid body resection in humans.FundingDK090541, HL120570

Exogenous L‐Arginine Restores Spontaneous Cardiac Baroreflex Sensitivity in Never‐Treated Hypertensive Men

Depressed cardiac baroreflex sensitivity (cBRS) is associated with an increased risk of mortality in patients with hypertension. A candidate mechanism for the centrally mediated impairment in cBRS is reduced synthesis of the neuromodulator nitric oxide. Therefore, we investigated the effect of intravenous L‐arginine, a precursor of nitric oxide, on the cBRS in human hypertension. Beat‐to‐beat blood pressure (Finometer) and heart rate (ECG) were measured in both normotensive (n=8, 44±4 yrs., Norm) and never‐treated hypertensive men (n=8, 47±2 yrs., Hyper) before and during intravenous infusion of L‐arginine (1 g/min; total, 30 g) or saline. Linear regression analysis between RR interval and systolic blood pressure was used to determine the gain (i.e. sensitivity) of the arterial baroreflex control of the heart. Compared to Norm group, patients with hypertension had lower spontaneous cBRS (Norm: 13±1 vs. Hyper: 7.9±1 ms.mmHg‐1; P&lt;0.01). On administration of L‐arginine, cBRS increased in both groups (Norm: 17±3 vs. Hyper: 15±3 ms.mmHg‐1; P&lt;0.01 vs. before infusion) and returned to near resting values after infusion. Increases in cBRS during infusion of L‐arginine were greater in Hyper (P&lt;0.05) and differences between groups disappeared. Importantly, during saline infusion, the spontaneous cBRS remained unchanged in both groups. In conclusion, these data demonstrate that short‐term L‐arginine infusion restores the arterial baroreflex control of heart rate in never‐treated hypertensive men, probably via increased nitric oxide synthesis.

SOD1 Overexpression Alters Aortic Depressor Nerve Function but Does not Protect Against Impairment of Baroreflex Heart Rate Control in Chronic Intermittent Hypoxia Exposed Mice

Mice overexpressing Cu/Zn Superoxide Dismutase (SOD1) have been used as a model for investigating effects of increased antioxidant activity in pathologies in which reactive oxygen species (ROS) play a role. Our objective in this study is to determine if human SOD1 overexpression can protect against dysfunction of aortic depressor nerve and baroreflex control of heart rate in chronic intermittent hypoxia (CIH) exposed mice. We used the transgenic mouse line C57B6SJL‐Tg (SOD1)2 Gur/J overexpressing human SOD1 and the non‐transgenic C57BL/6J mice (control). Mice (male, 4 months old, n=8‐9/group) were either maintained in room air (RA), or subjected to 6 minutes cycles of 21% and 5.7% O2 during 12‐h light cycles for 40‐50 days (CIH). Mice were anesthetized with isoflurane. Arterial blood pressure (ABP) and heart rate (HR) were measured from the femoral artery. Sodium nitroprusside (SNP) and phenylephrine (PE) were infused sequentially into the femoral vein to decrease and then increase ABP. Aortic depressor nerve activity (ADNA) was recorded. We found that: HR and mean arterial blood pressure (MABP) were similar between groups. Baroreflex control of HR in response to infusion of PE or SNP was not different in SOD1‐RA animals vs. C57‐RA, and it was decreased to a comparable extent in SOD1‐CIH and C57‐CIH. Recordings of ADNA in response to sequential SNP and PE injection‐induced blood pressure ramps revealed a significantly greater baroreceptor gain in SOD1‐RA compared to C57‐RA (p &lt; 0.01), but CIH exposure significantly decreased ADN baroreceptor gain in SOD1‐CIH compared to SOD1‐RA (P&lt;0.01). Our data suggests that SOD1 overexpression alters ADN function, but does not protect against CIH‐induced baroreflex impairment.

Abstract 15839: Effect of Serotonin Neuron Depletion on Arterial Blood Pressure Regulation in Young Rats

Infants dying of Sudden Infant Death Syndrome (SIDS) have reduced brainstem serotonin (5-hydroxytryptamine, 5-HT) where some cases die following episodes of severe bradycardia and hypoxemia. The specific role of central 5-HT in resting arterial blood pressure (BP) and on baroreflex sensitivity during neonatal life has not been studied. In adult animals, systemic depletion of 5-HT increases BP with no effect on heart rate (HR) and reduces the sensitivity of the baroreflex. Other studies have also shown that a loss of central 5-HT beginning in embryogenesis reduces resting BP and HR in adulthood. Based on these reports, we hypothesized that loss of brainstem 5-HT neurons in the neonatal period would reduce baseline BP and HR as well as reduce baroreflex gain. To test this, we utilized 3-week old Sprague Dawley rats treated centrally with 5,7-dihydroxytryptamine (5,7-DHT, n=4; ~120 ug in saline, i.c.v.), a chemical that is toxic to serotonergic neurons. Littermate controls were injected with saline (CTRL, n=5, ~3ul, i.c.v.). We measured BP with a femoral artery catheter. HR was derived from BP. Following a recovery period, we measured resting variables for 15 minutes and then injected phenylephrine (PE; 3mg/kg s.c.) followed by sodium nitroprusside (SNP; 2.5mg/kg s.c.), separated by 15 minutes, to induce pressor or depressor responses, respectively. For both responses, baroreflex gain was calculated as the [[Unable to Display Character: &amp;#8710;]]HR at the maximum [[Unable to Display Character: &amp;#8710;]]BP following drug injection. We found that a loss of 5-HT neurons did not alter baseline BP (p&gt;0.05) but did reduce baseline HR when compared to control littermates (p&lt;0.02). 5-HT neuron deficiency tended to reduce baroreflex gain in response to PE (CTRL: -2.756 ± 0.483 beats/mmHg; 5,7-DHT: -1.499 ± 0.348 beats/mmHg; p=0.058), but not SNP (CTRL: -2.408 ± 0.351 beats/mmHg; 5,7-DHT: -3.316 ± 1.214 beats/mmHg; p&gt;0.05). Our data indicate that brainstem 5-HT maintains resting HR, and is involved in baroreflex control of HR in response to hypertensive stimuli. Reduced brainstem 5-HT may predispose an infant to SIDS via altered autonomic control of BP and HR. The role of 5-HT in BP regulation during hypoxic conditions remains to be elucidated.

Temperature effects on baroreflex control of heart rate in the toad, Rhinella schneideri

For an adequate blood supply to support metabolic demands, vertebrates regulate blood pressure to maintain sufficient perfusion to avoid ischemia and other tissue damage like edema. Using a pharmacological approach (phenylephrine and sodium nitroprusside) we investigated baroreflex sensitivity at 15, 25, and 30°C in toads Rhinella schneideri. Baroreflex sensitivity presented a high thermal dependence (Q10=1.9–4.1), and the HR–baroreflex curve was shifted up and to the right as temperature increased from 15 to 30°C. Baroreflex variables, namely, HR range, gain50 (maximal gain) and normalized gain50 increased 206, 235, and 160% from 15 to 30°C, respectively. The cardiac limb of the baroreflex response to pharmacological treatments was significantly blunted after full autonomic blockade. In addition, there was a clear baroreflex–HR response mainly to hypotension at all three temperatures tested. These findings indicate that toads present temperature dependence for cardiac limb of the barostatic response and the cardiac baroreflex response in R. schneideri is primarily hypotensive rather than hypertensive as well as crocodilians and mammals. Thus, the cardiac baroreflex compensation to changes in arterial pressure might present different patterns among amphibian species, since the previously reported bradycardic compensation to hypertension in some anurans was not observed in the toad used in the present study.

Tonic arterial chemoreceptor activity contributes to cardiac sympathetic activation in mild ovine heart failure.

Heart failure (HF) is associated with a large increase in cardiac sympathetic nerve activity (CSNA), which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is increasing evidence that arterial chemoreceptor activation plays an important role in stimulating renal sympathetic nerve activity (RSNA) and muscle sympathetic nerve activity in HF. Given that sympathetic nerve activity to individual organs is differentially controlled, we investigated whether tonic arterial chemoreceptor activation contributes to the increased CSNA in HF. We recorded CSNA and RSNA in conscious normal sheep and in sheep with mild HF induced by rapid ventricular pacing (ejection fraction <40%). Tonic arterial chemoreceptor function was evaluated by supplementing room air with 100% intranasal oxygen (2-3 l min(-1)) for 20 min, thereby deactivating chemoreceptors. The effects of hyperoxia on resting levels and baroreflex control of heart rate, CSNA and RSNA were determined. In HF, chemoreceptor deactivation induced by hyperoxia significantly reduced CSNA [90 ± 2 versus 75 ± 5 bursts (100 heart beats)(-1), P < 0.05, n = 10; room air versus hyperoxia] and heart rate (96 ± 4 versus 85 ± 4 beats min(-1), P < 0.001, n = 12). There was no change in RSNA burst incidence [93 ± 4 versus 92 ± 4 bursts (100 heart beats)(-1), n = 7], although due to the bradycardia the RSNA burst frequency was decreased (90 ± 8 versus 77 ± 7 bursts min(-1), P < 0.001). In normal sheep, chemoreceptor deactivation reduced heart rate without a significant effect on CSNA or RSNA. In summary, deactivation of peripheral chemoreceptors during HF reduced the elevated levels of CSNA, indicating that tonic arterial chemoreceptor activation plays a critical role in stimulating the elevated CSNA in HF.

Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure.

Heart failure (HF) is associated with increased cardiac and renal sympathetic drive, which are both independent predictors of poor prognosis. A candidate mechanism for the centrally mediated sympathoexcitation in HF is reduced synthesis of the inhibitory neuromodulator nitric oxide (NO), resulting from downregulation of neuronal NO synthase (nNOS). Therefore, we investigated the effects of increasing the levels of NO in the brain, or selectively in the paraventricular nucleus of the hypothalamus (PVN), on cardiac sympathetic nerve activity (CSNA) and baroreflex control of CSNA and heart rate in ovine pacing-induced HF. The resting level of CSNA was significantly higher in the HF than in the normal group, but the resting level of RSNA was unchanged. Intracerebroventricular infusion of the NO donor sodium nitroprusside (SNP; 500 μg · ml(-1)· h(-1)) in conscious normal sheep and sheep in HF inhibited CSNA and restored baroreflex control of heart rate, but there was no change in RSNA. Microinjection of SNP into the PVN did not cause a similar cardiac sympathoinhibition in either group, although the number of nNOS-positive cells was decreased in the PVN of sheep in HF. Reduction of endogenous NO with intracerebroventricular infusion of N(ω)-nitro-l-arginine methyl ester decreased CSNA in normal but not in HF sheep and caused no change in RSNA in either group. These findings indicate that endogenous NO in the brain provides tonic excitatory drive to increase resting CSNA in the normal state, but not in HF. In contrast, exogenously administered NO inhibited CSNA in both the normal and HF groups via an action on sites other than the PVN.

Beneficial effects of physical activity on baroreflex control in the elderly.

The baroreflex mechanisms, by controlling autonomic outflow to the heart and circulation, contribute importantly to neural circulatory control. The main function of the baroreflex is to prevent wide fluctuations in arterial blood pressure and to maintain the physiological homeostasis under basal resting conditions and in response to acute stress. Baroreflex-mediated changes in autonomic outflow affect heart rate, myocardial contractility, and peripheral vascular resistance. The baroreflex control of heart rate is of particular interest in pathological conditions, since it has been associated with increased propensity for cardiac mortality and sudden death. Aging is associated with significant cardiovascular modifications. The changes in baroreflex function that occur with age have been systematically studied by several methodological approaches. The available evidence indicates a reduced arterial baroreflex control of heart rate favoring an increase in sympathetic and a decrease in parasympathetic drive to the heart as well as an impairment in the baroreceptor control of blood pressure. Both kinds of changes have resultant clinical implications. Exercise training can modulate the age-related decline in baroreflex function and the attending abnormalities in autonomic control, thus accounting for some of the beneficial effects of physical activity in reducing the risk of cardiovascular morbidity and mortality.

Deactivation of carotid body chemoreceptors by hyperoxia decreases blood pressure in hypertensive patients

Previous studies have shown that hyperoxia-induced deactivation of carotid body chemoreceptors reduces sympathetic activity in hypertensive patients but it does not affect blood pressure. The maintenance of blood pressure can be explained by the direct, vasoconstrictive effect of hyperoxia, which offsets diminished sympathetic activity. This study compares the effect of acute hyperoxia on hemodynamic parameters between hypertensive and normotensive subjects. Twelve males with hypertension (age 39.4±2.4 years; body mass index 27.4±1.1 kg m(-2)) and 11 normotensive males (age 39.9±2.7 years; body mass index 25.4±0.7 kg m(-2)) received, via non-rebreathing mask ventilation, ambient air, followed by 100% oxygen for 20 min. The stroke volume, heart rate, cardiac output, blood pressure, total peripheral resistance, respiratory rate, baroreceptor control of heart rate and oxygen saturation were recorded continuously. Several 30 s periods were analyzed before, during and after inducing hyperoxia. At baseline, the hypertensive subject's blood pressure was higher and their baroreflex control of heart rate was lower when compared with the normotensive control group. After the first 30 s of hyperoxia, systolic, diastolic and mean blood pressures, as well as the total peripheral resistance, decreased significantly in hypertensives but not in normotensives. After 20 min of 100% oxygen ventilation, systolic and mean blood pressures and total peripheral resistance was increased in hypertensive patients, and the cardiac output and stroke volume had decreased in both groups. The results of this study confirm that deactivation of carotid body chemoreceptors can acutely decrease blood pressure in humans.

Selective expression of an angiotensin‐(1‐7)‐producing fusion protein in the brain decreases blood pressure (1130.22)

Angiotensin‐(1‐7) [(Ang‐(1‐7)] attenuates arterial hypertension and improves baroreflex control upon chronic infusion in the central nervous system. In the present study we evaluated the baseline levels, variability and circadian pattern of blood pressure (BP) and heart rate (HR), as well as, the sensitivity of baroreflex control of heart rate and level of cardiac autonomic tone in transgenic rats that exhibit increased expression of Ang‐(1‐7) (TG) in the brain. Sprague‐Dawley (control group ‐ CTL) and TG rats were instrumented with telemetry probe to measure BP (DataScience). In other animals, baroreflex bradycardia (through injection of phenylephrine) and cardiac autonomic tone (by sequential and alternating blockade of β‐adrenergic and muscarinic receptors) were assessed using direct BP recordings (Biopac System). TG rats showed a lower basal mean BP (97 ± 2 mmHg vs 103 ± 2 mmHg in CTL, during the day and 101 ± 2 mmHg vs 106 ± 2 mmHg in CTL, during the night, n=13‐15), without a significant alteration in baseline HR. However, TG rats presented an increased cardiac sympathetic tone (156 ± 6 beats/ min vs 94 ± 10 beats/ min, in CTL, n=6) without change the intrinsic HR. There was a trend to a decrease in vagal tonus of TG rats (31 ± 7 beats/ min vs 53 ± 11 beats/ min in CTL; p&lt;0.15, n=6). In addition, no significant changes in the baroreflex bradycardia was observed. These data suggest that TG rats with a life time increase in Ang‐(1‐7) in the brain present an important change in BP and a direct or compensatory change in autonomic activity.Grant Funding Source: Support by PRONEX and INCT‐Nanobiofar Grants (CNPq and FAPEMIG) and CAPES

Do kappa opioid receptors regulate cardiovascular responses to severe haemorrhage in conscious newborn lambs? (859.3)

Previously, we showed that activation of kappa opioid receptors (KORs) influences systemic haemodynamics and the baroreflex control of heart rate (HR) in conscious lambs. The endogenous ligand for KORs, Dynorphin, is increased in response to severe blood loss however, any role for KORs in the haemodynamic responses to haemorrhage in the newborn is not known. In the present study, mean, systolic and diastolic arterial pressures (MAP, SAP, DAP) as well as HR were measured for 30 min before (Control) and 60 min after 30% haemorrhage in conscious lambs (aged ~one week, N=7) after pretreatment with vehicle (experiment one) or the selective KOR antagonist, GNTI (experiment two). After vehicle, MAP fell from 75±5 (Control) to 48±9 mmHg by 10 min after haemorrhage and remained decreased. This response resulted from a decrease in both SAP and DAP and was not altered by pretreatment with GNTI. HR decreased from 189±29 (Control) to 139±30 beats/min 10 min after haemorrhage; this response was attenuated by GNTI. Therefore, KORs do not appear to influence the blood pressure response to severe blood loss early in life but do abrogate the HR response to haemorrhage.Grant Funding Source: Supported by the CIHR.

Hypertension impairs spontaneous baroreflex heart rate control during exercise and muscle metaboreflex activation (1132.9)

Spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) is reduced in proportion to exercise intensity and magnitude of MMA. In hypertension (HTN), while SBRS is reduced at rest, the effect of exercise and MMA are unknown. In eight conscious dogs we measured SBRS in the control of HR (sequence method) at rest, during mild dynamic exercise, and during MMA (via imposed reductions of hindlimb blood flow), in the same animals before and 38±7 days after induction of HTN (via unilateral partial renal artery occlusion). HTN increased resting mean arterial blood pressure from 94±3 to 142±14 mmHg. In control, with the transition from rest to exercise, SBRS decreased from ‐4.01±0.77 to ‐2.38±0.61 bpm/mmHg and reduced further to ‐1.78±0.43 with MMA. In HTN, SBRS was significantly reduced at rest (‐2.38±0.34), during exercise (‐1.05±0.12) and MMA (‐0.90±0.14).We conclude that in HTN SBRS in the control of HR is impaired to similar degrees at rest, during exercise and MMA.Grant Funding Source: HL‐55743 and HL‐095819

Angiotensin AT2 receptors and the baroreflex control of renal sympathetic nerve activity

Angiotensin AT2 receptors and the baroreflex control of renal sympathetic nerve activity