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PubMed2000

The gain of the baroreflex bradycardia is reduced by microinjection of NMDA receptor antagonists into the nucleus tractus solitarii of awake rats.

The baroreflex activation with phenylephrine infusion produces a bradycardic response. In the present study, the role of NMDA receptors in the nucleus tractus solitarii (NTS) in the processing of the parasympathetic component of the baroreflex was evaluated using acid phosphonivaleric (AP-5), a selective NMDA receptor antagonist. Baroreflex activation was performed before and after bilateral microinjection of AP-5 into the intermediate commissural NTS (0.5 mm lateral to the midline). Microinjection of the vehicle (saline, 0.9%) or a dose of 2 nmol/50 nl of AP-5 into the NTS produced no effect on the gain of the baroreflex while a dose of 10 nmol/50 nl of AP-5 produced a significant reduction in the gain of the baroreflex 2 min after microinjection [-1.43+/-0.22 vs. -0. 43+/-0.03 bpm/mmHg, (n=6)], with a return to control levels 10 min after the microinjections. The dose of 10 nmol/50 nl was selective for NMDA receptors considering that the cardiovascular responses to microinjection of AMPA (0.05 pmol/50 nl), a non-NMDA receptor agonist, were not affected by this dose of AP-5 and the responses to microinjection of NMDA (2 nmol/50 nl) were blocked. The data show that the bradycardic response to baroreflex activation was blocked by AP-5 microinjected into the NTS, indicating that the neurotransmission of the parasympathetic component of the baroreflex is mediated by NMDA receptors in the NTS.

2-Amino-5-phosphonovalerate↗
PubMed1999

Ethanol abolishes clonidine-induced impairment of baroreflex control of heart rate in conscious rats.

Our previous studies showed that the ability of ethanol or clonidine to alter the baroreflex control of heart rate (baroreflex sensitivity, BRS) depends on the functional activity of aortic baroreflexes. In this study, we investigated the interaction between the two drugs on BRS in conscious rats with intact baroreflexes (shamoperated, SO) and after aortic baroreceptor denervation (ABD). The slope of the curve relating increments in mean arterial pressure induced by phenylephrine to corresponding reflex bradycardic responses was taken as an index of BRS. Ethanol (1 g/kg i.v.) significantly (p < 0.05) attenuated BRS in SO rats (-1.7 +/- 0.13 versus -1.04 +/- 0.15 beats/min/mm Hg) but not in ABD rats. Clonidine (30 microg/kg, i.v.) elicited significantly (p < 0.05) greater hypotensive responses in conscious ABD compared with SO rats. The BRS was not affected by clonidine administration in SO rats but showed significant (p < 0.05) reductions in ABD rats. Ethanol (1 g/kg, i.v.) had no effect on the hypotensive response to subsequently administered clonidine in ABD and SO rats; however, the effect of the two drugs on BRS was variable. In ABD rats, the BRS values before and after administration of ethanol and clonidine were similar, suggesting that pretreatment with ethanol counteracted clonidine-evoked attenuation of BRS in this rat preparation. In SO rats, the ethanol-clonidine combination produced a significant (p < 0.05) decrease in BRS, similar to the effect of ethanol when administered alone. These data confirm earlier findings that the aortic baroreflex arc modulates the interaction of ethanol and clonidine with baroreflex function. Further, the ability of ethanol to abolish clonidine-induced attenuation of BRS in ABD rats may relate to the compound effects of the two drugs on neuronal pathways participating in the central processing of baroreflexes in these rats.

Animals↗
PubMed2001

Percutaneous transluminal mitral valvuloplasty improves cardiopulmonary baroreflex sensitivity in patients with mitral stenosis.

Patients with heart failure frequently have increased sympathetic tone, which could result in part from impairment of the inhibitory influence of cardiopulmonary baroreflexes. Percutaneous transluminal mitral valvuloplasty (PTMV) provides a unique model for evaluating functional changes in cardiopulmonary baroreflexes without open-heart surgical manipulation. We examined the effects of PTMV on cardiopulmonary baroreflexes and sympathetic nerve activity in 10 patients with mitral stenosis. We measured muscle sympathetic nerve activity using microneurography. Cardiopulmonary baroreflex provocation was performed by applying a lower body negative pressure of -10 mm Hg, and its sensitivity was determined by dividing the percent change in muscle sympathetic nerve activity by the change in central venous pressure. Response to isometric exercise was assessed by handgrip at 30% of maximal voluntary contraction for 3 min. PTMV significantly increased mitral valve area and cardiac index and decreased mean left atrial pressure. PTMV significantly decreased burst rate from 25.1+/-2.5 to 15.6+/-2.6 bursts/min (p < 0.01) and burst incidence from 37.1+/-3.7 to 23.6+/-3.3 bursts/100 heart beats (p < 0.01). After PTMV, cardiopulmonary baroreflex sensitivities measured using burst rate and burst incidence were -39.9+/-4.9%/mm Hg and -38.7+/-6.2%/mm Hg, respectively, which were significantly steeper than those before PTMV (-9.2+/-1.1%/mm Hg and -8.4+/-1.1%/mm Hg; p < 0.01). There were significant correlations between muscle sympathetic nerve activity at rest and cardiopulmonary baroreflex sensitivity. PTMV did not affect muscle sympathetic responses to handgrip exercise. These results suggest that patients with mitral stenosis have baseline sympathetic nerve activation, which could result in part from impaired cardiopulmonary baroreflexes.

Adult↗
PubMed1998

Reproducibility of three different methods of measuring baroreflex sensitivity in normal subjects.

1. Baroreflex sensitivity is a useful tool for investigating cardiovascular reflexes in a number of clinical settings. Several different methods of measuring baroreflex sensitivity are available. In order to determine a clinically useful non-invasive method of measuring baroreflex sensitivity we compared two methods (spectral analysis and the Valsalva manoeuvre) with regard to reproducibility, agreement with a standard invasive method (phenylephrine infusion) and failure rate.2.Twenty-six healthy subjects aged 22 to 63 years attended on three separate occasions for measurement of baroreflex sensitivity using the different methods. The effect of a recent head-up tilt on baroreflex sensitivity was measured.3. Reproducibility was best for the low-frequency component of the spectral method [coefficient of variation 25.0% (range 3.5-42.4%)] and worst for the Valsalva method [coefficient of variation 29.3% (range 13.8-93.1%)]. Both non-invasive methods overestimated values compared with the phenylephrine method [bias of low-frequency component of the spectral method, 1.17 (0.38-3.6); bias of the Valsalva method, 1.13 (0.19-6.7)]. The high-frequency component of the spectral method did not agree with the phenylephrine method.4. The spectral analysis method had the fewest failures (seven subjects with a failure on at least one occasion), and the phenylephrine method the most (16 subjects with a failure on at least one occasion). A short head-up tilt did not affect the subsequent non-invasive measurement of baroreflex sensitivity.5. It was concluded that the low-frequency component of the spectral method was the most clinically useful non-invasive measurement of baroreflex sensitivity.

Adult↗
PubMed2003

Spontaneous 'baroreflex sequences' occur as deterministic functions of breathing phase.

Parallel increases or decreases of systolic pressures and R-R intervals occur spontaneously in healthy resting humans, and are thought to be expressions of vagal baroreflex physiology. We studied ten healthy supine young adults, and tested the null hypothesis that spontaneous baroreflex sequences are distributed uniformly throughout the breathing cycle. We recorded the electrocardiogram, photoplethysmographic arterial pressure, respiration (pneumobelt), and peroneal nerve muscle sympathetic activity in supine subjects who breathed spontaneously, or held their breaths in inspiration after 2 min of hyperventilation with 100% oxygen. We analysed pairs of three or more increasing or decreasing systolic pressures and R-R intervals with linear regression, and related the gain and timing of the onset of such sequences to the phase of respiration, and to preceding muscle sympathetic nerve activity. We found that baroreflex sequences occur erratically, at a frequency about one-third that of breathing. However, when baroreflex sequences do occur, the timing of their onset is dictated by the phase of respiration. Parallel increases of systolic pressures and R-R intervals ('up' sequences) begin just before and after the beginning of expiration, and parallel decreases of systolic pressures and R-R intervals ('down' sequences) begin during late expiration and inspiration. Average gains of up and down baroreflex sequences triggered by muscle sympathetic bursts are comparable during breathing and apnoea. However, the latencies between sympathetic bursts and baroreflex sequences are less during breathing than during apnoea. We propose that parallel systolic pressure--R-R interval sequences are expressions of arterial baroreflex physiology, and that the nearly fixed timing of such sequences within breaths reflects simply respiratory gating of muscle sympathetic bursts.

Adult↗
PubMed2000

Comparison between invasive and non-invasive measurements of baroreflex sensitivity; implications for studies on risk stratification after a myocardial infarction.

AIMS: The ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study has proved the independent prognostic value of baroreflex sensitivity. A limitation of the traditional method of estimating baroreflex sensitivity by phenylephrine, is the need to monitor intra-arterial blood pressure. Our objective was to establish whether this invasive method of monitoring could be superseded by non-invasive methods, such as the Finapres device. METHODS AND RESULTS: Patients with three repeated invasive and non-invasive baroreflex sensitivity measurements were selected from the ATRAMI database (n = 454). The mean of these measurements was taken as the baroreflex sensitivity estimate. The repeatability of both methods (standard deviation of the three measurements) decreased with increasing baroreflex sensitivity. There was no constant bias between invasive and non-invasive measurements (0. 22+/-2.2 ms. mmHg(-1), P = 0.42). The linear correlation was very high (r = 0.91, P < 0.01). The normalized 95% limits of agreement were -0.5 and 0.52. On survival analysis, invasive and non-invasive baroreflex sensitivity gave similar prognostic information (likelihood ratio: 155.6 (P = 0.007) and 155.0 (P = 0.006); risk ratio: 0.79 and 0.81, respectively). According to the ATRAMI cut-off points, 85% of patients were classified concordantly by the two methods. None of the patients at high (low) risk with the invasive method were classified as low (high) risk class by the non-invasive method. CONCLUSION: Despite wide limits of agreement, invasive and non-invasive baroreflex sensitivity measurements are highly correlated and provide equivalent prognostic information.

Autonomic Nervous System↗
PubMed2002

Spontaneous baroreflex sensitivity in young and older people during voluntary and electrically evoked isometric exercise.

BACKGROUND: In young people, cardiovagal baroreflex sensitivity alters during isometric exercise. We investigated whether the reduced resting baroreflex sensitivity seen with increasing age is similarly altered during exercise. METHODS: Cardiovagal baroreflex sensitivity was examined in 8 young (age+/-SEM, 25+/-1.7 years) and 9 older (61+/-3.0 years) subjects, using sequence analysis during voluntary and electrically evoked isometric exercise (at 30% maximum voluntary strength) and during subsequent post-exercise circulatory occlusion. RESULTS: In all phases of both conditions, baroreflex sensitivity was significantly reduced in the older group compared with the young group. (Median (interquartile range), voluntary 7.0 (4.4) vs 3.6 (3.8) ms x mmHg(-1), post-exercise circulatory occlusion 9.0 (8.2) vs 4.6 (4.0) ms x mmHg(-1); electrically evoked 6.6 (10.6) vs 3.2 (3.6) ms x mmHg(-1), post-exercise circulatory occlusion 8.3 (7.7) vs 2.9 (2.2) ms x mmHg(-1), young vs older respectively; P<0.05.) There was a marked rightward shift (resetting) of the baroreflex during exercise with the exception of electrically evoked in the older group. CONCLUSION: Our data demonstrate that the reduction in baroreflex sensitivity in older people is maintained during exercise and during post-exercise circulatory occlusion. Resetting of the baroreflex in the older subjects during moderate voluntary isometric calf exercise is largely the result of central command.

Adult↗
PubMed2005

Baroreflex control of heart rate during and after propofol infusion in humans.

BACKGROUND: This study was designed to determine cardiovagal baroreflex gain during propofol infusion and to characterize its recovery profile using the pharmacological and spontaneous sequence methods in 13 healthy volunteers without cardiovascular or autonomic disorders. METHODS: After an 8- to 10-h fast and no premedication, measurements of RR intervals obtained from the electrocardiogram and non-invasive beat-to-beat systolic blood pressure (SP) were made at conscious baseline, at 60 and 120 min after induction of general anaesthesia using propofol, and at 20, 60, 120 and 180 min after emergence from anaesthesia. During propofol anaesthesia, ventilation was mechanically controlled to maintain normocapnia and calculated propofol concentration was adjusted by a TCI system at 5 microg ml(-1). Baroreflex responses were triggered by bolus i.v. injections of phenylephrine and nitroprusside to alter SP by 15-30 mm Hg. The linear portions of the baroreflex curves relating RR intervals and SP by least-square regression analysis were determined to obtain pharmacological gains. In addition, spontaneous sequence baroreflex gains were calculated from spontaneously fluctuating SP and RR intervals. RESULTS: Baseline pressor and depressor test gains before propofol anaesthesia were 29.1 (SD 14.9) and 12.5 (7.8) ms mm Hg(-1), respectively. They were significantly depressed by 65-73% during propofol infusions. Similarly, baseline up- and down-sequence baroreflex gains were 33.8 (28.9) and 27.3 (19.8) ms mm Hg(-1), respectively, and were significantly depressed by 71-87% during propofol anaesthesia. Pressor test and up-sequence baroreflex gains returned to the baseline values 20 min after emergence from propofol anaesthesia, but depressor test and down-sequence baroreflex gains did not recover until 60 min after emergence. CONCLUSIONS: We conclude that heart rate responses to both lowering and elevating blood pressure were depressed by propofol anaesthesia, and 60 min was required for their full recovery after discontinuation of propofol infusion.

Adult↗
PubMed1998

Interaction of bradykinin and angiotensin-(1-7) in the central modulation of the baroreflex control of the heart rate.

OBJECTIVE: Previous studies have shown that angiotensin-(1-7) potentiates the vascular actions of bradykinin. In the present study, we evaluated the interaction of bradykinin and angiotensin-(1-7) in the central modulation of baroreflex control of the heart rate. MATERIALS AND METHODS: Blood pressure and reflex bradycardia, elicited by intravenous injection of phenylephrine, were evaluated in conscious male Wistar rats before and at the end of 1 h of an intracerebroventricular infusion of angiotensin-(1-7) at 0.5 or 1.0 microg/h combined with bradykinin at 2.5 microg/h; or angiotensin-(1-7) at 2.0 microg/h combined with bradykinin at 4.0 microg/h; or angiotensin-(1-7) alone at 2.0 or 4.0 microg/h; or bradykinin alone at 4.0 or 8.0 microg/h; or saline at 8 microl/h. In addition, baroreflex bradycardia was evaluated before and at the end of 1 and 2 h of intracerebroventricular infusion of angiotensin-(1-7) at 4 microg/h for 2 h; or saline at 8 microl/h in the first hour followed by HOE 140 at 90 ng/h in the second hour; or angiotensin-(1-7) at 4 microg/h in the first hour followed by angiotensin-(1-7) at 4 microg combined with HOE 140 at 90 ng/h in the second hour; or HOE 140 at 90 ng/h in the first hour followed by HOE 140 at 90th ng/h combined with angiotensin-(1-7) at 4 microg/h in the second hour; or saline at 8 microl/h for 2 h. RESULTS: The intracerebroventricular infusion of angiotensin-(1-7) or bradykinin alone required a dose of 4.0 and 8.0 microg/h, respectively, to facilitate baroreflex control of the heart. However, a simultaneous infusion of these peptides at subeffective rates was able to produce a significant increase in baroreflex sensitivity. In addition, the facilitation of the baroreflex control of the heart rate induced by angiotensin-(1-7) at 4.0 microg/h was inhibited by HOE 140. CONCLUSIONS: These results suggest that centrally, bradykinin and angiotensin-(1-7) can interact in order to modulate baroreflex control of the heart rate. In addition, our data indicate that the central modulatory effect of angiotensin-(1-7) on the baroreflex is mediated, at least in part, by the release of kinins.

Adrenergic beta-Antagonists↗
PubMed2001

Involvement of imidazoline receptors in the baroreflex effects of rilmenidine in conscious rabbits.

OBJECTIVE: It has been suggested that imidazoline receptors rather than alpha2-adrenoceptors are involved in the sympathoinhibitory action of centrally acting antihypertensive drugs such as rilmenidine. In the present study, we examined the relative importance of alpha2-adrenoceptors and imidazoline receptors in modulating the renal sympathetic and heart rate (HR) baroreflex in response to central administration of rilmenidine in conscious normotensive rabbits. METHODS: In seven conscious rabbits, chronically instrumented with a fourth ventricular (4V) catheter, aortic and vena caval cuff occluders and a renal nerve electrode, we continuously recorded renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and HR and assessed baroreflex MAP-RSNA and MAP-HR relationships with balloon-induced ramp rises and falls in MAP. Rabbits were treated with 4V rilmenidine (22 microg/kg) followed by 4V idazoxan (30 microg/kg; a mixed alpha2-adrenoceptor and imidazoline receptor antagonist) or 4V 2-methoxy-idazoxan (1 microg/kg; an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors). RESULTS: Rilmenidine lowered blood pressure by 24% and reduced both upper and lower plateaus of the renal sympathetic baroreflex curve, such that the RSNA range (difference between plateaus) was reduced by 40% (-32 +/- 10 normalized units). Curves were shifted to the left with the fall in MAP. Idazoxan restored MAP, maximum RSNA and the RSNA baroreflex range. By contrast the alpha2-adrenoceptor antagonist 2-methoxy-idazoxan caused only a partial recovery of MAP and RSNA baroreflex upper plateau and range (-9 +/- 2 mmHg, 29 and 33% lower than control). Both antagonists partially restored the HR baroreflex. CONCLUSION: These findings suggest that in conscious rabbits, both imidazoline receptors and alpha2-adrenoceptors are involved in the central antihypertensive and baroreflex actions of rilmenidine, but that activation of imidazoline receptors is more important for its renal sympathoinhibitory action.

Adrenergic alpha-Agonists↗
PubMed2002

The BK channel beta1 subunit gene is associated with human baroreflex and blood pressure regulation.

BACKGROUND: The baroreflex, which is important for the minute-to-minute regulation of blood pressure and heart rate, is influenced by genetic variance. Ion channels are important to baroreflex afferent and efferent function. Mice missing the beta1 subunit of the Ca2+-sensitive potassium channel (BK) are hypertensive and have a reset baroreflex. We tested the hypothesis that variants in the gene (KCNMB1) coding for the BK beta1 subunit are associated with baroreflex function. METHODS: We studied six single-nucleotide polymorphisms (SNPs) in KCNMB1. RESULTS: Four SNPs in intron 3, exon 4a, exon 4b and exon 4c gave significant results. For instance, exon 4b SNP AA individuals had higher heart rate variability, compared to CA, or CC persons, in particular in the high-frequency range. The low-frequency range showed no association. Consistent with the heart rate variability data, homozygous AA persons had greater baroreflex slopes than CA or CC persons, also in the high-frequency range. These associations could not be shown in the low-frequency range for heart rate variability and baroreflex slopes. CONCLUSIONS: These data support the notion that variants in channel genes may be responsible for the great range in heart rate variability and baroreflex function observed in humans. Such variation may also play a role in the development of hypertension.

Adult↗
PubMed2002

Sympathetic and cardiac baroreflex function in panic disorder.

BACKGROUND: Recent reports have demonstrated increased cardiac risk, and an association with essential hypertension in patients with panic disorder. The cause is not known, but possibly involves sympathetic nervous activation. In this study, we evaluated the arterial baroreflex control of vascular sympathetic nervous outflow and cardiac baroreflex function in panic disorder patients. METHODS AND RESULTS: We studied nine patients suffering from panic disorder and ten healthy subjects. Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of blood pressure (BP) and electrocardiogram (ECG). The relationship between MSNA and spontaneous diastolic BP (DBP) changes was assessed at rest and was defined as the arterial baroreflex control of MSNA. Cardiac baroreflex function was assessed using the sequence method. Anxiety was assessed using Spielberger's anxiety state and trait inventory. The slopes of the relationship between MSNA and DBP were more negative (steeper) in the panic disorder group compared with the control subjects (-5.97 +/- 0.45 versus -3.06 +/- 0.43 bursts/100 heart beats per mmHg, P < 0.001). Panic disorder patients had significantly higher state and trait anxiety scores. The slope of the relationship between MSNA and diastolic BP was significantly related to the trait anxiety of the subjects. There was no difference between the cardiac baroreflex sensitivity between the two groups. CONCLUSION: Patients with panic disorder exhibit enhanced reflex gain of the arterial baroreflex control of MSNA but no change in the cardiac baroreflex. While any clinical significance this observation might have in relation to increased cardiac risk in panic disorder, or to concordance with essential hypertension, remains to be elucidated, increased reactivity of vasoconstricting sympathetic nerves may be a trait characteristic in this cohort.

Adult↗
PubMedDate not supplied

Baroreflex control of heart rate during hypoxia and hypercapnia in chronically hypertensive rabbits.

1. It has been proposed that hypertension alters the respiratory and cardiovascular responses to chemoreceptor stimulation. However, in studies of human hypertension or in genetic animal models of hypertension it has been difficult to unequivocally attribute the changes to hypertension per se, rather than to a genetic predisposition towards an altered chemoreflex response independent of hypertension. 2. In the present study a group of seven rabbits were made hypertensive via a continuous 7 week infusion of angiotensin II (AngII; 50 ng/kg per min, i.v.). Animals were studied twice before AngII treatment commenced, twice during infusion and 48 h after stopping infusion. At each of these times the relationship between heart rate (HR) and mean arterial pressure (MAP) was determined under normoxic, acute hypoxic (10% O2 + 3% CO2) and acute hypercapnic (18% O2 +, 6.5% CO2) conditions for 20 min. A group of six animals also served as time controls. 3. Angiotensin II infusion increased arterial pressure from control levels of 80 +/- 2 to 114 +/- 8 mmHg and maintained it at this level throughout the 7 week period. After 1 week of AngII infusion there was a rightward shift in the heart rate-baroreflex curve, indicating that the baroreflex was now operating at an increased level of pressure. These changes were associated with reductions in the gain from -7.6 +/- 1.6 to -3.0 +/- 0.2 b.p.m./ mmHg, HR range and curvature of the baroreflex. These effects were maintained throughout the 7 weeks of hypertension and were reversed within 2 days of ceasing AngII infusion. Acute hypoxia and hypercapnia in normotensive animals caused a reduction in the HR range of 19 +/- 7 and 15 +/- 7 b.p.m., respectively, but caused no change in the gain (sensitivity) of the baroreflex. Despite the marked changes in the baroreflex produced by the hypertension, the effect of hypoxia or hypercapnia on the HR baroreflex was not different in the hypertensive group. 4. It is concluded that chronic experimental AngII-based hypertension does not alter the HR baroreflex response to hypoxia or hypercapnia and suggests that the altered responses seen in other studies is due to a genetic predisposition as opposed to the effect of raised arterial pressure.

Angiotensin II↗
PubMed1999

Hypoxia inhibits baroreflex vagal bradycardia via a central action in anaesthetized rats.

It is known that arterial baroreflexes are suppressed in stressful conditions. The present study was designed to determine whether and how hypoxia affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia. In chloralose-urethane-anaesthetized rats, baroreflex vagal bradycardia was evoked by electrical stimulation of the aortic depressor nerve, and the effect of 15 s inhalation of hypoxic gas (4% O2) was studied. Inhalation of hypoxic gas was found to inhibit baroreflex vagal bradycardia. The inhibition persisted after bilateral transection of the carotid sinus nerve. Cervical vagus nerves were cut bilaterally and their peripheral cut ends were stimulated to provoke vagal bradycardia of peripheral origin so as to determine whether hypoxia could inhibit vagal bradycardia by acting on a peripheral site. In contrast to baroreflex vagal bradycardia, the vagus-induced bradycardia was not affected by hypoxic gas inhalation. It is concluded that baroreflex vagal bradycardia is inhibited by hypoxia and the inhibition is largely mediated by its direct central action.

Animals↗
PubMed1996

Baroreflex resetting but no vascular tolerance in response to transdermal glyceryl trinitrate in conscious rabbits.

1. We investigated whether acute (5 h) and chronic (3 days) transdermal glyceryl trinitrate (GTN) patches could cause the development of tolerance in terms of haemodynamics and vascular reactivity in the conscious rabbit. The effects of haemodynamic tolerance were assessed on arterial pressure, heart rate and the baroreflex control of heart rate, while hindquarter vascular reactivity in response to dilator and constrictor drugs and reactive hyperaemia were used to assess vascular tolerance. 2. Seven days prior to experiments, an inflatable cuff, a pulsed Doppler flow probe and an indwelling intra-aortic catheter (for i.a. agonist infusions) were implanted around the lower abdominal aorta. 3. In acute experiments, the effects of 0-5 h treatment with transdermal GTN (0 Sham), 10 or 20 mg 24 h-1) on MAP, HR and the baroreflex were examined. Chronic experiments were performed on three separated days (days 0 - before, 4 - with GTN patch and 8 - recovery). On each day, the baroreflex, reactive hyperaemic responses and hindquarter vascular dose-response curves to i.a. GTN, adenosine, acetylcholine, S-nitroso-N-acetylpenicillamine (SNAP) and methoxamine were assessed. On days 1-4, GTN was administered transdermally via a patch(es) (10 mg 24 h-1 (low dose) or 20 mg 24 h-1 (high dose); renewed every 24 h). 4. Acute treatment with 20 mg GTN 24 h-1, but not with 0 (n = 4) or 10 mg GTN 24 h-1 (n = 4), caused a significant fall in MAP (8 +/- 1 mmHg; n = 4) and resetting of the baroreflex by 5 h. Chronic GTN caused a significant fall in MAP of 8 +/- 2 and 8 +/- 2 mmHg on day 4 with low (n = 8) and high dose (n = 8), respectively, with no change in HR. There was no significant change to hindquarter vascular reactivity to i.a. infusion of GTN, nor were there any significant differences in the reactivity to i.a. adenosine, acetylcholine, SNAP or methoxamine with either low or high doses of GTN. 5. Chronic GTN treatment with low and high dose patches caused a parallel leftward shift ('resetting') of the baroreflex on day 4. By day 8, the baroreflex had still not recovered from this leftward shift 6. In the rabbit, chronic exposure to clinical nitrate patches caused haemodynamic compensation and baroreflex resetting but no evidence of vascular reactivity tolerance. Novel NO donor drugs and delivery regimens which provide intermittent dosing may prevent the development of haemodynamic resetting rather then preventing vascular tolerance, a commonly perceived difficulty in chronic nitrate therapy.

Administration, Cutaneous↗
PubMed1994

Baroreflex sensitivity: methods, mechanisms, and prognostic value.

A large bulk of data collected over the last 25 years links reflex autonomic activation during acute myocardial ischemia with risk of developing lethal arrhythmias. Specifically, evidence obtained in an experimental preparation in chronically infarcted dogs supported the concept that sympathetic hyperactivity enhances likelihood for ventricular tachyarrhythmias, vagal activation exerts protective effects. Based on this knowledge, it was first proposed by our group that analysis of autonomic control of heart rate could provide information relevant to risk stratification in post-myocardial infarction individuals. Among several possibilities, baroreflex sensitivity was evaluated by correlating blood pressure rise induced by bolus injections of phenylephrine with the consequent beat to beat R-R interval lengthening. Experimental studies involving direct recordings from single neural vagal fibers directed to the heart documented that baroreflex sensitivity closely reproduces cardiac vagal activity. In a large group of conscious dogs it was shown that a depressed baroreflex sensitivity was highly predictive of the risk for ventricular, fibrillation during acute myocardial ischemia. The clinical prognostic value of baroreflex sensitivity has already been confirmed in pilot studies conducted by different groups of investigators. Overall, the phenylephrine test has been performed in several hundred patients with no reports of side effects. An ongoing multicenter study, the ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) is aimed to definitively assess the predictive value of baroreflex sensitivity and heart rate variability in patients with a prior myocardial infarction. While the enrollment is still ongoing, this study has already provided an important methodological information about the possibility of using non invasive technique to record blood pressure by means of FINAPRES, to evaluate baroreflex sensitivity. Comparison among 142 tests performed with simultaneous recording from an intraarterial line and from FINAPRES indicated a strong correlation (r = 0.9) between the two methods. ATRAMI is expected to close the enrollment in the near future. To data, baroreflex sensitivity appears to be a safe and non-invasive test likely to provide meaningful information on autonomic balance and consequently on risk profile of patients with a prior myocardial infarction.

Animals↗
PubMed2005

Arterial baroreflex resetting during exercise: a current perspective.

Within the past 20 years numerous animal and human experiments have provided supportive evidence of arterial baroreflex resetting during exercise. In addition, it has been demonstrated that both the feedforward mechanism of central command and the feedback mechanism associated with skeletal muscle afferents (the exercise pressor reflex) play both independent and interactive roles in the resetting of the arterial baroreflex with exercise. A fundamental alteration associated with baroreflex resetting during exercise is the movement of the operating point of the reflex away from the centring point and closer to the threshold, thereby increasing the ability of the reflex to buffer hypertensive stimuli. Recent studies suggest that central command and the cardiopulmonary baroreceptors may play a role in this movement of the operating point on the baroreflex-heart rate and baroreflex-blood pressure curve, respectively. Current research is focusing on the investigation of central neural mechanisms involved in cardiovascular control, including use of electrophysiological and molecular biological techniques in rat and mouse models to investigate baroreflex resetting as well as use of state of the art brain imaging techniques in humans. However, the purpose of this review is to describe the role of the arterial baroreflex in the regulation of arterial blood pressure during physical activity from a historical perspective with a particular emphasis on human investigations.

Baroreflex↗
PubMed2003

Acute shifts of baroreflex control of renal sympathetic nerve activity induced by treadmill exercise in rats.

The present study aimed to investigate whether there was a resetting of the baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) during exercise. Wistar female rats (n = 11) were chronically implanted with catheters for the measurement of systemic arterial (Pa) and central venous pressures and with electrodes for measurement of RSNA and electrocardiogram (ECG) at least 3 days before study. The baroreflex curve for RSNA was determined by changing Pa using rapid intravenous infusions of phenylephrine and nitroprusside. The baroreflex response curves for RSNA and HR were characterized by an inverse sigmoid function curve from which the response range, gain, centering point and minimum response were estimated. Exercise shifted the Pa-RSNA baroreflex curve upward and to the right and was associated with increases in response range of 122 +/- 44 % (P < 0.05), maximum response of 173 +/- 40 % (P < 0.05), maximum gain of 149 +/- 66 % (P < 0.05) and midpoint pressure of 15 +/- 5 mmHg (P < 0.05) compared with the pre-exercise level. After cessation of exercise, the Pa-RSNA baroreflex curve was suppressed vertically with a significant decrease in maximum response of 57 +/- 14 % (P < 0.05) compared with the pre-exercise level. These data suggest that the right-upward shift of baroreflex control of sympathetic nerve activity may play a critical role in raising and stabilizing Pa during exercise. The suppression of the baroreflex control of sympathetic nerve activity may partly explain the post-exercise inhibition of sympathetic nerve activity and contribute to the post-exercise hypotension.

Adrenergic alpha-Agonists↗