Reduced heart rate variability and baroreflex sensitivity in primary biliary cirrhosis.

BACKGROUND: Standardized mortality ratio for primary biliary cirrhosis (PBC) is 2.87. Even after accounting for liver and cancer-related deaths there is an unexplained excess mortality associated with PBC. We have assessed heart rate variability (HRV) and baroreflex sensitivity (BRS) risk factors associated with cardiovascular mortality, in 57 PBC patients and age- and sex-matched normal controls. METHODS: HRV and BRS were measured non-invasively in subjects and controls. Beat to beat RR interval and 'Portapres' blood pressure data were processed using power spectral analysis. Power was calculated in very low frequency (VLF), low-frequency (LF) and high-frequency (HF) bands according to international guidelines. BRS (alpha) was computed using cross-spectrum analysis. Patients also underwent fatigue severity assessment using a measure validated for use in PBC. RESULTS: PBC patients had significantly lower total HRV compared with controls (P=0.02), with the reduction occurring predominantly in the LF domain (P=0.03). BRS was also significantly reduced compared with controls (P=0.02). There were no significant differences in HRV or BRS between cirrhotic and non-cirrhotic patients. Within the PBC patient group HRV was significantly lower in fatigued than in non-fatigued patients (P<0.05). CONCLUSION: Abnormalities of HRV and BRS in PBC are not specific to advanced disease but are associated with fatigue severity. Abnormalities could be associated with increased risk of sudden cardiac death, potentially contributing to the excess mortality seen in PBC.     

Analysis of baroreflex control of heart rate in conscious dogs with pacing-induced heart failure

The autonomic components of the baroreflex control of heart rate were evaluated in conscious mongrel dogs before and after 4-6 weeks of ventricular pacing (250 beats/min). Arterial baroreflex sensitivity (BRS) was determined by the slopes of linear regression of pulse interval versus the preceding systolic arterial pressure in response to bolus injections of either phenylephrine or nitroglycerin. BRS was significantly depressed in the heart failure state [nitroglycerin slope, 5.0 +/- 2.7 (mean +/- SD) versus 16.6 +/- 5.1 msec/mm Hg, p less than 0.005; phenylephrine slope, 15.0 +/- 14.8 versus 32.0 +/- 26.7 msec/mm Hg, p less than 0.005]. There was no depression in BRS in dogs that were used as time controls or were acutely paced for 30 minutes. After beta 1-adrenergic blockade with metoprolol, the resting heart rate in the heart failure state was depressed more than in the normal state (-17.0 +/- 5.0% versus -3.2 +/- 3.4%, p less than 0.001). Atropine significantly increased resting heart rate more in the normal state than in the heart failure state (115.8 +/- 36.7% versus 25.4 +/- 14.5%, p less than 0.005). Thus, dogs in the heart failure state appear to have high resting cardiac sympathetic tone and low resting vagal tone. For nitroglycerin administration, metoprolol depressed BRS by 47.6 +/- 26.3% in the normal state and by 63.6 +/- 58.5% in the heart failure state. Atropine decreased the BRS by 86.7 +/- 7.8% in the normal state and by 39.5 +/- 30.2% in the heart failure state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clonidine improves spontaneous baroreflex sensitivity in conscious mice through parasympathetic activation

Alpha-2 adrenoceptors are important in baroreflex regulation. We tested the impact of alpha-2 adrenoceptors on heart rate variability (HRV) and spontaneous baroreflex sensitivity (BRS) in conscious mice with telemetry (TA11PA-C20). Baseline beat-to-beat measurements (2 hours between 8:00 am to 12:00 pm) were compared with measurements after intraperitoneal alpha-2 adrenoceptor blockade (yohimbine 2 mg/kg) and alpha-2 adrenoceptor stimulation (clonidine 1, 10, and 50 mg/kg). Blood pressure (BP) was 128+/-6/87+/-6 mm Hg and heart rate (HR) was 548+/-18 bpm at baseline. BRS, calculated with the cross-spectral method, was 1.2+/-0.1 ms/mm Hg at baseline. BP increased 20+/-2/13+/-2 mm Hg with yohimbine. HR increased by 158+/-23 bpm. BRS did not change. BP decreased 16+/-7/5+/-4 mm Hg with 1 mg/kg of clonidine and did not change with a higher dose. HR decreased with clonidine (176+/-28, 351+/-21, 310+/-29 bpm during 1, 10, and 50 mg/kg of clonidine, P<0.01). HRV (total power=4629+/-465, 7002+/-440, and 6452+/-341 ms2 during 1, 10, and 50 mg/kg of clonidine, P<0.01) and BRS were profoundly increased with clonidine (14+/-1, 13+/-1, and 10+/-1 ms/mm Hg, P<0.01). The effects of clonidine were abolished with atropine (2 mg/kg plus 50 mg/kg of clonidine) but not with metoprolol (4 mg/kg plus 50 mg/kg of clonidine). These data suggest that alpha-2 adrenoceptors exert a regulatory influence on autonomic cardiovascular control and baroreflex function. The effect of clonidine on baroreflex HR regulation is mediated by the parasympathetic nervous system. These murine data fit well with recent human observations regarding parasympathetic activation via alpha-2 adrenoceptors.     

氯沙坦对心肌梗死大鼠压力反射敏感性的影响

目的通过测定实验心肌梗死大鼠压力反射敏感性及口服氯沙坦对压力反射敏感性的作用,探讨血管紧张素Ⅱ受体拮抗剂对心肌梗死后自主神经功能的影响。方法开胸结扎大鼠冠状动脉制作心肌梗死模型,采用新福林法测定假手术安慰剂大鼠和心肌梗死安慰剂大鼠术后3天和28天的压力反射敏感性水平。氯沙坦组大鼠给予氯沙坦5mg/kg/天灌胃,28天时进行压力反射敏感性测定。结果手术后3天和4周时,两假手术组大鼠压力反射敏感性无明显差异。两心肌梗死组大鼠压力反射敏感性也无显著差异,但较假手术组明显降低(P<0.01);氯沙坦组大鼠压力反射敏感性较心肌梗死组明显增加(P<0.01),与假手术组差异无显著性意义。线性回归分析显示压力反射敏感性与心率、平均动脉压、左心室舒张末压之间无相关性。结论心肌梗死大鼠在术后3天时压力反射敏感性显著降低并持续至4周。氯沙坦能够增加心肌梗死大鼠的压力反射敏感性,而且这种影响独立于其改善血流动力学作用之外。     

Opiate receptor inhibition improves the blunted baroreflex function in conscious dogs with right-sided congestive heart failure

The endogenous opiate system is activated in congestive heart failure. because endogenous opioids are known to depress the baroreflex function, we conducted studies to determine whether the increased endogenous opioids play a role in causing the reduced baroreflex function that occurs in heart failure. Right-sided congestive heart failure was produced in 16 dogs by tricuspid avulsion and progressive pulmonary artery constriction. Seven sham-operated dogs were included for comparison. Baroreflex function was measured in the conscious dogs after pretreatment with either normal saline or an opiate-receptor antagonist by bolus administration of phenylephrine. The slope of the regression line relating systolic blood pressure to cardiac cycle (R-R) interval was taken as an index of baroreflex sensitivity. Plasma beta-endorphin was elevated in the dogs with heart failure (15.3 +/- 2.5 pmol/l) compared with the sham-operated dogs (4.2 +/- 0.4 pmol/l, p less than 0.001). The dogs with heart failure also exhibited a reduced baroreflex sensitivity (3.84 +/- 0.19 msec/mm Hg) after saline pretreatment when compared with the sham-operated dogs (10.86 +/- 1.20 msec/mm Hg, p less than 0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16 +/- 0.26 msec/mm Hg (p less than 0.01) but produced no significant effects in sham-operated dogs (11.36 +/- 1.42 msec/mm Hg). To further study the site of action for the effect of naloxone, we measured baroreflex sensitivity in the dogs with heart failure after pretreatment with naloxonazine, a selective mu-receptor antagonist, with ICI 154,129, a selective delta-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)     

Short-term effects of naloxone hemodynamics and baroreflex function in conscious dogs with pacing-induced congestive heart failure

Objective. The purpose of this study was to determine the effects of naloxone on systemic hemodynamics and reflex function in dogs with congestive heart failure induced by rapid pacing.Background. We have shown previously that naloxone, an opiate receptor antagonist, improves cardiac output, aortic blood pressure, systolic performance and the baroreflex function in conscious dogs with chronic right-sided congestive heart failure. However, whether endogenous opioids also play a role in mediating the reduction of myocardial and baroreflex function in animals with left heart failure remains controversial.Methods. We administered naloxone (1 mg/kg body weight) and normal saline solution to 15 dogs with pacing-induced congestive heart failure (225 beats/min for 8 weeks) and 11 control dogs. In addition to systemic hemodynamic measurements, the slope of pressure-area relation obtained from echocardiography with intravenous bolus injection of phenylephrine was taken as a load-independent index of myocardial contractility. Baroreflex function was estimated by the slope of the regression line relating systolic aortic pressure and RRE interval.Results. Plasma beta-endorphin levels were elevated in dags with congestive heart failure. Naloxone administration increased heart rate, mean aortic pressure, first derivative of left ventricular pressure, cardiac output and myocardial contractility in pacing-induced congestive heart failure. These changes correlated significantly with basal plasma beta-endorphin levels and were accompanied by increases in plasma beta-endorphin and catecholamines after naloxone administration. However, unlike the hemodynamic and cardiac effects of naloxone, baroreflex function did not change after naloxone in dogs with congestive heart failure.Conclusions. The increase in basal plasma beta-endorphin suggests that the endogenous opiate system is activated in lef-tsided congestive heart failure. Because naloxone improves the systemic hemodynamics and myocardial contractile function under this condition, the endogenous opioids appear to play an important role in mediating the myocardial depression that occurs in heart failure. However, the endogenous opiate system has no apparent effect on the regulation of baroreflex control in heart failure induced by rapid pacing.     

Depressed responsiveness to vasoconstrictor and dilator agents and baroreflex sensitivity in conscious, newborn lambs.

The effects of vasoconstrictors and vasodilators were compared in conscious, newborn lambs and adult sheep instrumented with electromagnetic flow probes on the ascending aorta and catheters in the thoracic aorta. Methoxamine, angiotensin II, norepinephrine, nitroglycerin and isoproterenol were administered intravenously to evaluate their effects on arterial pressure, cardiac output and systemic vascular resistance (SVR). The difference in response between adults and newborns was most apparent with methoxamine. Methoxamine, 400 micrograms/kg, i.v., which increased mean arterial pressure by 57 +/- 6% and SVR by 278 +/- 27% in newborn lambs, caused greater increases (p less than 0.01) of 81 +/- 8% and 1418 +/- 141%, respectively, in the adults. Responses also differed significantly between newborn and adult animals to norepinephrine, angiotensin II, nitroglycerin and isoproterenol. In a second group of animals in which smaller amounts of methoxamine and isoproterenol were injected directly into the terminal aorta, changes in terminal aortic flow and resistance were examined. Again, both vasoconstrictor and vasodilator responses were more marked in adults than in newborns. Finally, the sensitivity of the arterial baroreceptor reflex was evaluated by comparing the regression of pulse interval (PI) on systolic arterial pressure (SAP) after an intravenous dose of methoxamine in conscious, adult and newborn animals. The PI/SAP slopes in adult sheep, 45.4 +/- 3.5 msec/mm Hg, were significantly greater (p less than 0.01) than in newborn lambs, 11.7 +/- 2.2 msec/mm Hg.     

Effect of salt loading on baroreflex sensitivity in reduced renal mass hypertension

Background: High dietary salt, as well as renal mass reduction, is known to decrease baroreflex sensitivity in rats. However, the effect of high salt intake on baroreflex sensitivity is unknown in reduced renal mass (RRM) hypertension; therefore, the aim of this study was to investigate the effects of salt loading on arterial baroreflex sensitivity and mean arterial pressure (MAP) in RRM hypertension.

Methods: Both RRM and sham-operated control (SO) rats were loaded with 0.25 or 0.5% NaCl for five weeks. Plasma Na⁺, K⁺, and creatinine levels were measured, and baroreflex sensitivity was evaluated before and after β₁ blockade. In addition, cardiac vagal tone and intrinsic heart rate (IHR) were measured. RESULTS: RRM decreased full baroreflex sensitivity of the tachycardic response under 0.5% NaCl loading and the parasympathetic bradycardic response under 0% NaCl loading. The NaCl loading did not affect the severity of RRM hypertension. Cardiac vagal tone and IHR decreased in RRM rats versus SO controls under all NaCl loading conditions. RRM decreased plasma K⁺ under 0% NaCl loading and increased plasma Na⁺ under 0.5% NaCl loading. High (0.5%) NaCl loading decreased IHR and increased plasma creatinine and left ventricular weight in RRM rats. CONCLUSIONS: RRM in combination with 0.5% NaCl loading led to a decrease in the sensitivity of full baroreflex and of the parasympathetic component of baroreflex. Changes in plasma Na⁺ and K⁺ levels, due to NaCl loading, may have contributed to the decrease in baroreflex sensitivities and IHR but had no effect upon MAP in RRM rats.     

Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease

Objectives: Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS.

Materials and methods: We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery.

Results: Integrated BRS was reduced in patients [7.00 (5.80–9.25) vs. 11.1 (8.50–14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.54?±?1.20 vs. 4.48?±?1.43?ms/10^?3). FMD was higher in patients (9.81?±?3.77 vs. 5.59?±?1.36%). FMD and neural BRS were directly related in controls (r?=?0.62), but inversely related in patients (r?=?–0.49).

Conclusions: Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation.     

Bilateral atrial appendectomy abolishes increased plasma atrial natriuretic peptide release and blunts sodium and water excretion during volume loading in conscious dogs.

The atrial appendages contain most of the atrial natriuretic factor (ANF) in the mammalian heart, and atrial appendage mechanical function predicts ANF secretion during volume loading. To demonstrate the crucial role of the atrial appendages in ANF release, we first measured hemodynamics and changes in plasma ANF after injection of 1,000 ml i.v. normal saline in conscious dogs and again after bilateral atrial appendectomy; we next measured changes in renal function using infusions of atriopeptin 24 to achieve plasma levels corresponding to levels achieved during volume loading; and we lastly measured renal function during acute volume expansion and also after atrial appendectomy. Plasma ANF increased from 65 +/- 11 to 246 +/- 54 pg/ml after volume loading but did not increase after atrial appendectomy. Atrial appendectomy did not alter the tachycardia or hemodynamic effects of volume loading. Infusion of 10 ng/kg/min atriopeptin 24 increased plasma ANF from 50 +/- 9 to 234 +/- 54 pg/ml, increased urine output 34 +/- 10%, and increased sodium excretion 62 +/- 10% in dogs with intact atrial appendages. Renal function was compared in dogs before atrial appendectomy: 20, 40, and 60 minutes after volume loading, urine flow rate increased by 5.9 +/- 0.5, 6.9 +/- 0.4, and 4.4 +/- 0.8 ml/min, while sodium excretion increased by 717 +/- 60, 839 +/- 84, and 582 +/- 57 mueq/min. After atrial appendectomy urine flow rate increased 2.1 +/- 0.7, 2.7 +/- 0.7, and 2.0 +/- 0.6 ml/min, and sodium excretion increased only by 327 +/- 110, 324 +/- 77, and 340 +/- 92 mueq/min (p less than 0.01) during volume loading.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intracoronary infusion of prostaglandin I2 attenuates arterial baroreflex control of heart rate in conscious dogs

Prostaglandin I2 (PGI2) is known to stimulate ventricular C fiber receptors resulting in a Bezold-Jarisch-like reflex. Also, cardiac receptor stimulation is known to interact with the expression of arterial baroreflexes. Therefore, experiments were performed to determine the effects of left circumflex coronary artery infusion of PGI2 on the baroreflex control of heart rate in conscious instrumented dogs. Dogs were instrumented chronically with an aortic catheter for the measurement of mean aortic pressure, hydraulic occluder cuffs on the descending aorta and inferior vena cava, a left ventricular catheter for the measurement of left ventricular pressure and heart rate, and a nonocclusive catheter in the left circumflex coronary artery. At the time of experimentation, arterial pressure was altered randomly in steps by partially inflating the occluders. Mean arterial pressure-heart curves (baroreflex curves) were constructed by fitting the data to a logistic curve by nonlinear regression. PGI2 infused into the left circumflex coronary artery at doses of 10, 20, and 50 ng/kg/min caused significant (p less than 0.05) inhibition of the maximum heart rate, heart rate range, and maximum slope of the curve compared to the control baroreflex curve obtained during intracoronary infusion of PGI2 vehicle. PGI2 had no significant effect on the minimum heart rate during hypertension. Since PGI2 is known to stimulate left ventricular receptors, these effects were most likely produced via stimulation of cardiac receptors. In additional experiments using beta 1-blockade with metoprolol or cholinergic blockade with atropine methyl bromide, it was shown that PGI2 attenuates baroreflex-mediated tachycardia by preventing parasympathetic withdrawal completely and by attenuating sympathetic stimulation by approximately 50%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diastolic dysfunction and baroreflex sensitivity in hypertension.

The determinants of diastolic dysfunction in patients with systemic hypertension are not completely known. To evaluate the possible role of age, arterial blood pressure, and baroreflex heart rate response impairment in causing diastolic dysfunction, we studied 61 patients (42 male; mean+/-SD age, 43.9+/-12 years) with newly recognized and therefore previously untreated systemic hypertension. Diastolic dysfunction was evaluated by means of Doppler echocardiography (and diagnosed as such when the early to atrial peak velocity ratio corrected to heart rate was <1), arterial blood pressure by 24-hour ambulatory monitoring, and baroreflex heart rate response by means of the spectral technique (alpha index) during paced (0.27 Hz) and spontaneous breathing (in a supine position and during tilt). Nineteen patients had diastolic dysfunction, the most powerful predictor of which was age (r=-0.63, P<0.001). The patients with diastolic dysfunction had significantly lower values for spectral baroreflex gain in the high-frequency band than those without (5.2+/-3 versus 8.4+/-5 ms/mm Hg during paced breathing, P<0.05; 7. 4+/-4 versus 13.3+/-7 ms/mm Hg in a supine position, P<0.05; 4.3+/-4 versus 5+/-2 ms/mm Hg during tilt, P相似文献   

Sodium excretion in normal conscious dogs.

Bitches maintained on a low Na intake, were given doses of saline (0.125 mol.litre(-1) NaCl, 0.025 mol.litre(-1) NaHCO3, 0.004 mol.litre(-1) KCl) by stomach tube. Doses of 100 and 200 cm3 produced only minor increases in Na excretion; after 300 cm3, Na excretion rose from about 2 to about 60 micromol.min(-1). Plasma protein fell by 1.8 litre(-1) for each 100 cm3 of saline retained. Within normal ranges of Na excretion there is a threshold of plasma protein concentration above which Na is retained and below which Na is excreted. Changes in exogenous creatinine clearance were measured allowing calculation of the filtered load of Na, which shows that the absolute tubular reabsorption of Na and water is increased in volume expansion by isotonic saline. Meat produced large increase in glomerular filtration rate without much increase in Na excretion and mechanisms are discussed by which Na reabsorptin is more effective after meat than after doses of saline. Creatinine cleaerance increased by 0.67 cm3.min(-1) for each fall of 1 g.litre(-1) in plasma protein; this is predicted by a theory that the glomerular capillary blood pressure is 9.3 kPa (70 mmHg) rather than 6.7 kPa (50 mmHg).     

Increased sensitivity to isoprenaline following digoxin pretreatment in anaesthetised and conscious dogs

STUDY OBJECTIVE--The aim of the study was to evaluate the effect of chronic digoxin therapy on cardiac sensitivity to isoprenaline. DESIGN--Responses to isoprenaline were examined in both conscious and anaesthetised dogs pretreated with digoxin, and compared with conscious or anaesthetised controls with no digoxin pretreatment. Isoprenaline infusion (0.001-0.1 micrograms.kg-1.min-1) in pretreated groups was performed 7 d after digoxin dosing was stopped, when plasma digoxin concentrations were zero. SUBJECTS--Mongrel dogs of either sex (15-25 kg) were used in the experiments, done under anaesthetic. They were divided into three groups (n = 6 per group): group A were controls; groups B and C were pretreated with digoxin 500-750 micrograms.d-1, for 14 d (B) and 7 d (C). For the experiments in conscious animals, six mongrel dogs (25-30 kg) and two greyhounds (25-30 kg) were used; group D (n = 6) were treated with digoxin for 20-40 d; group E (n = 2) were treated for 7 d. MEASUREMENTS AND RESULTS--Heart rate, blood pressure and myocardial contractility (dP/dt: integrated isometric tension) were measured during isoprenaline infusion. Digoxin pretreatment for 14 d did not significantly change the chronotropic or depressor responses to isoprenaline in anaesthetised dogs but there was a 10-fold increase in inotropic sensitivity to isoprenaline following withdrawal. When the pretreatment period was reduced to 7 d there was no change in any of the responses to isoprenaline. In conscious dogs there was also a significant increase in inotropic sensitivity to isoprenaline after digoxin withdrawal, but this was not so marked as in anaesthetised dogs. In conscious dogs chronotropic sensitivity to isoprenaline was also increased. CONCLUSIONS--It is possible that the inotropic effect maintained during the 2 weeks of digoxin treatment may cause substantial withdrawal of sympathetic tone to the heart, with a consequent increase in beta adrenoceptor number or sensitivity, which could be detected a week after digoxin withdrawal.     

Analgosedation-enhanced baroreflex sensitivity in acute local myocardial ischaemia.

In acute local myocardial ischaemia produced in mongrel dogs, the sensitivity of baroreflex decreased as electrical instability (vulnerability) of cardiac ventricles increased. Simultaneous administration of a benzodiazepine and a powerful analgesic (analgosedation) augmented both baroreflex sensitivity and ventricular fibrillation threshold. Modulation of neurovegetative activation of the heart by drugs in the early stage of ischaemia holds promise as a potential technique of sudden coronary death prevention.     

Factors associated with baroreflex sensitivity: association with morning blood pressure.

Baroreflex sensitivity (BRS) is a primary mechanism for acute and chronic control of blood pressure (BP). However, there are few data showing the relationship between BRS and ambulatory BP (ABP). We assessed the hypothesis that BRS specifically contributes to some specific parameters of ABP in never-treated hypertensive/normotensive subjects. We studied 128 subjects (mean age: 54.5+/-13 years, 60% male) consisting of 92 untreated hypertensive and 36 normotensive subjects. Radial tonometric BP and simultaneous RR interval were recorded for 10 min, and the Valsalva maneuver was performed 3 times for each subject. BRS was calculated in two ways: the spontaneous-BRS by the spectral method, and the Valsalva-BRS by the slope method, using commercial software. ABP monitoring was performed on the same day as the BRS test. Of 128 subjects, we obtained BRS from 111 subjects with the Valsalva method and 123 subjects with the spontaneous method. Univariate analyses showed that the Valsalva-BRS was negatively correlated only with morning systolic BP (r=-0.21, p=0.03). Multivariable analyses showed that the Valsalva-BRS (ms/mmHg) was independently associated with the morning systolic BP (beta=-0.26, p=0.022), even after adjusting for age, sex, body mass index, presence of diabetes, duration of hypertension, clinic systolic BP and pulse rates. The spontaneous-BRS estimates were inversely correlated with clinic pulse rates in the same model. In conclusion, impaired BRS evaluated by the Valsalva method was associated with high morning BP level, independent of other confounders. Morning hypertension might be partly mediated by impaired BRS.     

Exercise training and baroreflex sensitivity in patients with neurally mediated syncope.

Neurally mediated syncope (NMS) is the result of a criticalcerebral hypoperfusion. The pathophysiology of this abnormalityis multifactorial. Optimal cerebral perfusion depends on anadequate functioning of the control mechanisms maintaining cerebraloxygen delivery.     

Adrenomedullin modulates the neurohumoral response to acute volume loading in normal conscious sheep

The physiological role of adrenomedullin (ADM) in volume and pressure homeostasis remains unclear. Accordingly, we assessed possible modulatory actions of ADM infusions on the neurohumoral response to acute volume loading with dextran in normal conscious sheep. Dextran (15 ml/kg), given with concurrent ADM (5.5 pmol/kg per min--raising plasma ADM from below detection to approximately 10 pmol/l) or vehicle control infusions, induced matched significant (P<0.001 by ANOVA) falls in hematocrit (27-30%) during both ADM and control and similar increases in right atrial pressure (approximately 10 mmHg). Compared with control, both systemic (P=0.033) and pulmonary (P=0.005) arterial pressure and peripheral resistance (P=0.004) were reduced during ADM but were raised post-infusion. The dextran-induced increase in cardiac output was augmented by ADM (P=0.048). Dextran-induced increases in plasma atrial natriuretic peptide (ANP; P=0.008), brain natriuretic peptide (BNP; P=NS) and cyclic guanosine monophosphate (cGMP; P=0.003) were augmented post-ADM infusions. The dextran-induced fall in plasma renin activity (PRA) was attenuated by ADM (P=0.039) whereas plasma aldosterone levels were unaltered. ADM augmented the increase in urinary volume during the second 2-h clearance period post-dextran. Our data indicate that ADM modifies the hemodynamic and hormonal response to an acute volume challenge, enhances natriuretic peptide secretion and reduces systemic vascular resistance. These results provide further evidence that ADM plays a physiological role in volume and pressure homeostasis.