Cardiopulmonary Baroreceptors Research Articles

Baroreflex control of muscle sympathetic nerve activity in borderline hypertension.

Patients with borderline hypertension have exaggerated vascular responses to orthostatic stress produced by tilt or lower body negative pressure (LBNP). It has been suggested that 1) in the supine position, these patients have augmented activity of cardiopulmonary baroreceptors that exerts an increased restraint on sympathetic vasoconstrictor tone; 2) withdrawal of this augmented inhibitory baroreceptor activity during orthostatic stress elicits augmented reflex sympathetic vasoconstrictor outflow; and 3) augmented cardiopulmonary baroreceptor activity may be secondary to impaired arterial baroreflex mechanisms. To test these hypotheses, we recorded muscle sympathetic nerve activity from the peroneal nerve in seven borderline hypertensive subjects and seven age-, sex-, and weight-matched normotensive subjects during three levels of nonhypotensive LBNP and infusions of phenylephrine and nitroprusside. During LBNP, reductions of central venous pressure were similar in borderline hypertensive and normotensive subjects, and arterial pressure and heart rate values were unchanged. Increases of sympathetic nerve activity, however, were significantly greater in borderline hypertensive than in normotensive subjects at each level of LBNP, indicating an augmented gain of the cardiopulmonary baroreflex. To determine whether this augmentation is related to impairment of arterial baroreflexes, we measured changes of sympathetic nerve activity during increases and decreases of arterial pressure produced with infusions of intravenous phenylephrine and nitroprusside. Central venous pressure was held at control levels by LBNP during phenylephrine and saline infusion during nitroprusside. Changes of sympathetic nerve activity during alterations of arterial pressure were similar in borderline hypertensive and normotensive subjects. These data show that cardiopulmonary baroreflex control of SNA is augmented in borderline hypertensive subjects and that this augmentation does not result from an attenuation of the arterial baroreflex.

Prolonged duration of myocardial ischemia in patients with coronary heart disease and impaired cardiopulmonary baroreceptor sensitivity.

To investigate the potential contribution of cardiopulmonary reflexes in myocardial ischemia, the coronary vascular response to cardiopulmonary baroreceptor unloading and the number and the duration of spontaneous episodes of symptomatic and asymptomatic myocardial ischemia were evaluated in 23 patients with coronary heart disease. Lower-body negative pressure at -10 mm Hg, which causes selective deactivation of cardiopulmonary receptors, reduced left ventricular filling pressure in all patients, but calculated coronary vascular resistance increased in only 14 patients (from 0.846 +/- 0.1 to 1.07 +/- 0.1 mm Hg/ml/min, p less than 0.01) (group 1). In the remaining nine patients, coronary resistance did not change during cardiopulmonary receptor unloading (group 2). A 60-mm Hg increase in neck tissue pressure, which induces arterial baroreflex-mediated sympathetic activation, caused comparable coronary vasoconstriction in the two groups. Clinical characteristics of the two groups were similar, except that a lower ejection fraction was measured in group 1 (45 +/- 2% vs. 56 +/- 1%, p less than 0.01). In the 14 patients in group 1, 24-hour electrocardiographic monitoring showed 151 episodes of myocardial ischemia (average individual value, 10.8 +/- 1), 137 of which were asymptomatic, with an individual daily ischemic period of 62 +/- 6 minutes. In contrast, the nine patients in group 2 had only symptomatic episodes of myocardial ischemia, and the daily ischemic period in these patients was longer than in patients of group 1 (104 +/- 10 minutes, p less than 0.01). After a 3-day treatment with digitalis, the patients of group 2 showed 38 asymptomatic episodes of myocardial ischemia and a shorter daily ischemic period (85 +/- 6 minutes, p less than 0.01 vs. control conditions). In contrast, no change in number and duration of the ischemic episodes was detected in group 1. The effects of acute administration of digitalis (Lanatoside-C 0.02 mg/kg body wt e.v.) on the coronary vascular response to cardiopulmonary receptor unloading were assessed in a separate group of patients with ischemic heart disease. Digitalis treatment did not significantly modify the magnitude of the coronary vascular response induced by -10 mm Hg lower-body negative pressure in the patients showing in control conditions an increase of coronary vascular resistance greater than 20% of the basal value during cardiopulmonary receptor unloading. On the contrary, digitalis potentiated the coronary reflex response to -10 mm Hg lower-body negative pressure in the patients with impaired cardiopulmonary responsiveness (delta percent increase in coronary vascular resistance: 1 +/- 1% in control conditions; 23 +/- 3.9% after digitalis, p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Direct neurohumoral evidence for isolated sympathetic nervous system activation to skeletal muscle in response to cardiopulmonary baroreceptor unloading.

It has been postulated that cardiopulmonary baroreceptor unloading in humans results in nonuniform activation of the sympathetic nervous system. We reasoned that simultaneous measurements of arterial and venous norepinephrine (NE) spillover and clearance (using NE kinetics), muscle sympathetic neural activity (using microneurography), forearm blood flow (using plethysmography), and skin blood flow (using laser Doppler velocimetry) during lower body negative pressure at -15 mm Hg would isolate the location and extent of cardiopulmonary baroreceptor-mediated sympathetic nervous system activation. We exposed normal subjects (n = 8) to lower body negative pressure for 30 minutes, with measurements obtained at baseline, 5-10 minutes (EARLY), and 25-30 minutes (LATE). We found that arterial NE spillover, reflecting systemic sympathetic nervous system activation, did not increase significantly, whereas arterial NE clearance decreased significantly. In contrast, forearm venous NE spillover, reflecting skin and muscle sympathetic nervous system activation, increased by 17% and muscle sympathetic neural activity by 35% EARLY, whereas venous clearance did not change significantly. Although laser Doppler skin blood flow did not change, plethysmographic forearm blood flow (combined muscle and skin blood flow) decreased by 28%. All changes were sustained throughout 30 minutes of lower body negative pressure. Our data suggest that sympathetic vasoconstriction to muscle is greater than it is to skin in response to cardiopulmonary baroreceptor unloading. Moreover, our data suggest that reduced NE clearance in the arterial circulation is the primary mechanism by which arterial NE concentrations rise. Conversely, NE spillover appears to be the primary mechanism responsible for increasing venous NE concentrations measured from the forearm during cardiopulmonary baroreceptor unloading.

Sympathoinhibitory effects of atrial natriuretic factor in normal humans.

In rats, atrial natriuretic factor (ANF) reduces sympathetic nerve activity (SNA) reflexively by sensitizing cardiac mechanoreceptors with inhibitory vagal afferents. We performed three series of experiments in 26 normal young men to document whether ANF inhibits SNA in humans and if so, to determine potential mechanisms for this phenomenon. First, we recorded muscle SNA before and during brief infusions of ANF, vehicle (saline solution), and sodium nitroprusside, titrated to achieve reductions similar to those produced by ANF in diastolic pressure and central venous pressure, and we also assessed the effect of ANF on sympathetic nerve responses to a cold pressor test (CPT). Second, we determined the effect of ANF on Doppler-derived measurements of cardiac output and responses to hypotensive (-40 mm Hg) lower-body negative pressure (LBNP) and its sudden cessation. Third, we applied nonhypotensive (-15 mm Hg) LBNP to selectively unload cardiopulmonary baroreceptors, and we released LBNP to stimulate these inhibitory afferents during sequential infusions of nitroglycerin, vehicle (saline solution), and ANF. Our key findings were that 1) reductions in arterial and central venous pressures during ANF infusion were not accompanied by anticipated reflex increases in muscle SNA; 2) ANF blunted the increase in SNA with CPT; 3) ANF increased stroke volume and cardiac output; and 4) sympathoneural responses to both the application and the sudden cessation of nonhypotensive LBNP were attenuated, not augmented, by ANF. Changes in plasma norepinephrine concentrations reflected these sympathetic nerve responses to ANF. These results do not support the concept that ANF inhibits sympathetic outflow reflexively in humans by increasing discharge from cardiac mechanoreceptors with inhibitory vagal afferents but are consistent with either a central or a ganglionic sympathoinhibitory action of ANF. ANF could facilitate hypotension and natriuresis in humans by attenuating the reflex sympathetic response to baroreceptor deactivation.

Baroreflex regulation of regional blood flow in congestive heart failure

In patients with congestive heart failure (CHF), the distribution of the cardiac output is altered. Cardiopulmonary and arterial baroreceptors normally can regulate regional blood flow, but their contribution in heart failure is not known. To examine the role of baroreceptors in the regulation of regional blood flow in CHF, the effect of lower body negative pressure (LBNP) on forearm, renal, and splanchnic blood flow was evaluated in 12 patients with heart failure. Incremental LBNP at -10 and -40 mmHg decreased central venous pressure but had not effect on systolic blood pressure or pulse pressure. Renal blood flow decreased from 505 +/- 63 to 468 +/- 66 ml/min during LBNP -10 mmHg (P less than 0.05) and to 376 +/- 74 ml/min during LBNP -40 mmHg (P less than 0.01). Splanchnic blood flow decreased from 564 +/- 76 to 480 +/- 62 ml/min during LBNP -10 mmHg (P less than 0.01) and to 303 +/- 45 ml/min during LBNP -40 mmHg (P less than 0.01). Forearm blood flow did not decrease during LBNP -10 mmHg or -40 mmHg. To determine whether the absence of limb vasoconstriction during LBNP was confined to abnormalities in the baroreflex arc or was secondary to impaired end-organ responsiveness, six patients with heart failure and six normal subjects received an intrabrachial artery infusion of phenylephrine. Phenylephrine increased forearm vascular resistance comparably in each group. These data demonstrate that baroreceptors can regulate splanchnic and renal but not limb vascular resistance in patients with congestive heart failure and may contribute to the redistribution of blood flow that occurs in this disorder.

Pathophysiologic levels of atrial natriuretic factor do not alter reflex sympathetic control: Direct evidence from microneurographic studies in humans

To determine if circulating levels of atrial natriuretic factor comparable with those seen in pathophysiologic states alter autonomic control of the circulation, direct recordings of hemodynamic variables and efferent sympathetic nerve activity to muscle (microneurography) were obtained during two separate protocols in a total of 21 normal men (age 25 +/- 1 years). In protocol 1, the responses of 10 men were compared during incremental mechanical unloading of cardiopulmonary baroreceptors with lower body negative pressure versus responses to comparable unloading during infusion of alpha-human atrial natriuretic factor. Lower body negative pressure decreased pulmonary artery diastolic and right atrial pressures, did not alter arterial pressure or heart rate and increased muscle sympathetic nerve activity from 205.2 +/- 36.3 to 438.7 +/- 100.2 units/min (p less than 0.01). Intravenous infusion of atrial natriuretic factor (25 ng/kg per min) increased plasma levels of the hormone from 24 +/- 4 to 322 +/- 34 pg/ml (p less than 0.01, n = 6), produced similar decreases in pulmonary artery diastolic and right atrial pressures, did not alter arterial pressure, increased heart rate and increased sympathetic nerve activity from 233.1 +/- 35.6 to 387.2 +/- 64.9 units/min (p less than 0.05). Thus, during similar hemodynamic perturbations produced by lower body negative pressure or infusion of atrial natriuretic factor at the dose used in this study, these subjects exhibited comparable sympathoexcitatory responses, with a 109 +/- 23% increase in sympathetic activity during lower body negative pressure and a 76 +/- 19% increase during atrial natriuretic factor infusion (p = NS). In protocol 2, the responses of 11 additional men were examined during lower body negative pressure performed before and again during infusion of atrial natriuretic factor (12.5 ng/kg per min). During baseline (prehormone) trials, lower body negative pressure (-14.5 +/- 1.6 mm Hg) decreased central venous pressure, did not change arterial pressure or heart rate and increased sympathetic nerve activity from 215 +/- 47.7 to 372.3 +/- 64.3 units/min (p less than 0.001). Infusion of atrial natriuretic factor increased plasma levels of the hormone from 39 +/- 8 to 313 +/- 18 pg/ml (p less than 0.01, n = 7); central venous pressure was held constant during hormone infusion by intravenous infusion of saline solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Sustained increases in sympathetic outflow during prolonged lower body negative pressure in humans

The purpose of this study was to determine whether prolonged unloading of cardiopulmonary baroreceptors with lower body negative pressure (LBNP) causes constant increases in sympathetic outflow to skeletal muscles. Eight healthy subjects underwent a 20-min control period followed by 20 min of 15-mmHg LBNP. This pressure was selected because it did not cause any significant change in mean arterial blood pressure (sphygmomanometry) or heart rate, suggesting that the cardiopulmonary baroreceptors were selectively unloaded and the activity of the arterial baroreceptors was unchanged. Muscle sympathetic nerve activity in the peroneal nerve (MSNA, microneurography) increased from an average of 21.8 +/- 1.7 bursts/min over the last 5 min of control to 29.0 +/- 2.9 bursts/min during the 1st min of LBNP (P less than 0.05 LBNP vs. control). The increase in MSNA observed during the 1st min was sustained throughout LBNP. Forelimb blood flow (plethysmography) decreased abruptly at the onset of the LBNP from a control value of 4.3 +/- 0.5 ml.min-1.100 ml-1 to 2.5 +/- 0.2 at the 1st min; the flow then increased and remained significantly above this value, but below the control value, throughout LBNP. Similar blood flow findings were obtained in additional studies, when the hand circulation was excluded during the flow measurements. Forearm skin blood flow (laser Doppler) also decreased abruptly at the onset of LBNP and was followed by partial recovery, but these changes were too small to account for all the increases in limb blood flow over the course of LBNP.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular control by arterial and cardiopulmonary baroreceptors in awake dogs with atrioventricular block.

We studied reflex responses to pressure changes at arterial and cardiopulmonary baroreceptors in five awake dogs with atrioventricular block before and after baroreceptor denervation. We changed ventricular pacing rate and blood volume to vary cardiac output and arterial (MAP) and central venous pressure (CVP). We determined peripheral resistance (TPR) and atrial rate (HRA) as responses. In the intact animal, regression analysis showed an average relationship across dogs of TPR = 169-0.69 MAP-1.952 CVP + error. Correlation (r) between observed and predicted TPR was 0.83. For HRA, regression indicated HRA = 291.66-2.319 MAP + 8.144 CVP + error (r = 0.899). TPR and MAP are percent of control at 90 beats/min; CVP is in mmHg; HRA, in beats/min. Although its coefficient is smaller, MAP explains approximately 69% of the variation in TPR. After arterial baroreceptor denervation, effects of MAP on TPR were insignificant and the coefficient for CVP increased. Subsequent vagal block eliminated all reflex responses. Effects from the two receptor sites sum linearly. They act cooperatively with changes in blood volume, but oppose one another with cardiac output changes.

Reduced Susceptibility to Syncope During Postural Tilt in Old Age

Clinical studies of syncope suggest a decreased prevalence of vasovagal syncope in old age. To examine this possibility and its pathophysiologic implications, we report the results of two studies. The first evaluated responses to head-up tilt in young and old subjects. Presyncopal vasovagal symptoms occurred in 4 of 9 young subjects and only 1 of 22 old subjects. The second study asked whether decreased beta-adrenergic responsiveness protected the old during tilt via unopposed alpha-adrenergic-mediated vasoconstriction. Blood pressure, heart rate, and forearm vascular resistance responses to tilt in 11 healthy young subjects randomized to receive intravenous propranolol hydrochloride or saline were compared with those of 10 healthy elderly. Propranolol attenuated heart rate and forearm vascular resistance responses. Vasovagal symptoms occurred in 4 young and no old subjects; 2 were symptomatic during propranolol administration. Thus, presyncopal vasovagal symptoms are less common during tilt in old age. Propranolol did not prevent the vasovagal reaction or enhance forearm vasoconstriction. Propranolol's attenuation of vasoconstriction may be due to decreased activation of cardiopulmonary baroreceptors during beta-blockade.

5 The importance of thirst in maintenance of fluid balance

Plasma osmolality is maintained within very narrow limits by the control of water intake via thirst and water output via secretion of vasopressin. Osmoreceptors are situated in the brain, but on the blood side of the blood-brain barrier in a circumventricular organ. These regions are stimulated by an increase in plasma osmolality and form the most important input to cause thirst and drinking. Cardiopulmonary and arterial baroreceptors sensitive to blood volume and blood pressure also can be important, so hypovolaemic events such as haemorrhage can stimulate thirst. Both raised plasma osmolality and reduced blood volume contribute to thirst and vasopressin secretion following water deprivation. The importance of the nucleus medianus in the neural circuitary involved in integrating thirst should be emphasized. Mechanisms which stop drinking are different from those which initiate it, and oropharyngeal metering of the volume of fluid consumed provides the important input. There are a number of situations in humans where thirst thresholds and sensitivities are altered. The elderly have higher thirst thresholds and this can cause symptoms of dehydration. Increased drinking is seen in congestive heart failure, renal hypertension and certain cerebral lesions. Thirst thresholds are set at lower levels in pregnancy and in the luteal phase of the menstrual cycle and may contribute to fluid retention in these situations.

Atrial Natriuretic Peptide Attenuates the Reflex Sympathetic Responses to Lower Body Negative Pressure

The authors studied the effect of intravenous infusion of atrial natriuretic peptide (ANP) on the plasma catecholamine and forearm vasoconstrictor responses to cardiopulmonary baroreflex deactivation in six normal, male volunteers in order to determine whether ANP influences reflex forearm vasoconstriction in humans. Unloading of low-pressure cardiopulmonary baroreceptors (CPBR) was accomplished by application of low levels (-10 and -20 mm Hg) of lower body negative pressure (LBNP). The authors measured the plasma norepinephrine (NE) and epinephrine, the mean arterial pressure (MAP), and the forearm vascular resistance (FVR) responses to reflex sympathetic activation by LBNP. ANP infusion (0.1 microgram.kg-1.min-1) decreased (p less than 0.01) basal MAP, as well as plasma renin activity and plasma aldosterone levels (p less than 0.05). ANP infusion also reduced (p less than 0.01) plasma NE responses to both levels of LBNP and tended to decrease both epinephrine and FVR during ANP infusion at -20 mm Hg LBNP (p = 0.8). These data suggest that exogenous ANP inhibits the reflex sympathetic responses that occur with CPBR unloading. The blunted plasma NE responses to CPBR unloading parallel the attenuation of FVR response to LBNP during ANP infusion, despite significant LBNP-induced hypotension.

Regional vascular responses to prolonged lower body negative pressure in normal subjects.

The purpose of this study was to determine the effects of sustained unloading of baroreceptors in humans. The regional hemodynamic responses to lower body negative pressure (LBNP) were determined in 20 normal subjects. LBNP at -10 mmHg for 1 h decreased central venous pressure (CVP) without affecting blood pressure or heart rate, suggesting that only cardiopulmonary baroreceptors were unloaded. Forearm blood flow (FBF) and splanchnic blood flow (SBF) both decreased. Renal blood flow (RBF) did not change, but glomerular filtration rate (GFR) increased. Plasma renin activity rose slightly, whereas plasma norepinephrine levels did not change. Peak LBNP (either -20 or -40 mmHg for 1 h) caused a further decline in CVP and narrowed pulse pressure, thus unloading both arterial and cardiopulmonary baroreceptors. FBF returned to base-line values and SBF decreased further. RBF fell and the GFR remained increased. Plasma renin activity increased further, and plasma norepinephrine level rose. Thus the forearm and splanchnic circulations are sensitive to sustained unloading of cardiopulmonary baroreceptors; renal vasoconstriction occurs with additional unloading of arterial baroreceptors. Renin-angiotensin system activation during LBNP may be pertinent to the preservation of glomerular filtration.

Low dose of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis: Evidence for an impaired cardiopulmonary baroreflex function

High doses of nitroglycerin may decrease portal pressure in patients with cirrhosis with untoward effects such as arterial hypotension and a decrease in systemic O2 uptake. In the present study, low doses of nitroglycerin (7 to 15 micrograms per min, i.v.) were administered in 11 patients with cirrhosis in order to unload cardiopulmonary baroreceptor--one of the possible mechanisms by which nitroglycerin may improve splanchnic hemodynamics--and moreover to avoid deleterious systemic effects. Nitroglycerin significantly decreased right atrial pressure (-35%) and pulmonary wedged pressure (-27%) with significant increase in plasma norepinephrine concentration (+23%), which indicated that cardiopulmonary baroreceptor unloading was achieved. Changes in systemic hemodynamics were slight, although significant, with a decrease in arterial pressure (-8%) and an increase in heart rate (+8%); this indicates a minimal effect on high-pressure baroreflexes. In contrast, no significant change was observed in hepatic venous pressure gradient, hepatic blood flow and azygos blood flow. However, the fraction of cardiac output reaching the azygos system significantly increased by 18%. Plasma renin activity did not change significantly. Moreover, O2 transport and uptake were significantly decreased. These findings show that low doses of nitroglycerin failed to improve splanchnic hemodynamics in patients with cirrhosis. These results suggest an impaired cardiopulmonary baroreflex function which is probably located on the efferent arch.

Neurohumoral and hemodynamic effects of lower body negative pressure in patients with congestive heart failure

Baroreflex modulation of forearm vascular resistance (FVR) has been reported to be abnormal in patients with congestive heart failure (CHF). However, the neurohumoral mechanisms for this impairment are not defined. We assessed the responses of arterial pressure, FVR, plasma norepinephrine, and plasma renin activity to lower body negative pressure in 29 patients with compensated CHF (New York Heart Association class III and IV) and in 11 normal age-matched control subjects. Baseline mean arterial pressure (83 ± 2 vs 84 ± 2 mm Hg) and mean arterial pressure during LBNP (−10, −20, and −40 mm Hg) were not significantly different in the two groups. Basal FVR (43.7 ± 4 vs 27 ± 2 units), plasma norepinephrine (605 ± 81 vs 155 ± 8 pg/ml), and plasma renin activity (8.3 ± 1.7 vs 1.2 ± 0.2 ng/ml/hr) were significantly ( p < 0.01) higher in patients with CHF. The relative increases in FVR responses during LBNP of −10, −20, and −40 mm Hg (10 ± 4% vs 70 ± 12%, 17 ± 6% vs 106 ± 21%, and 24 ± 9% vs 152 ± 28%) were markedly attenuated in patients with CHF compared to control subjects. Plasma norepinephrine and plasma renin activity responses during LBNP were also attenuated in patients with heart failure. Our results suggest that baroreflex control of FVR and plasma norepinephrine and plasma renin activity is impaired in CHF because of the inability of the cardiopulmonary baroreceptors to alter sympathetic outflow.

Abnormalities of sympathetic vasomotor tone in distal axonal neuropathy

Microneurographic studies have shown that sympathetic vasomotor nerve activity is observed less frequently in patients with peripheral neuropathy than in controls, but when detected its pattern and the baroreflex latencies appear to be normal. Vasomotor nerve function was examined in chloralose-urethane anaesthetised dogs by comparing the discharge of renal sympathetic nerves in control animals and animals with acrylamide neuropathy. There was a normal pattern of pulse related inhibition of sympathetic nerve activity as well as normal amplitude spontaneous compound nerve action potentials in the animals with neuropathy. When vasomotor tone was altered abruptly by raising pressure in a bilateral isolated carotid sinus preparation, the baroreflex latencies were normal in the affected animals. However, when carotid sinus pressure was kept constant, pulse-related sympathetic inhibition, normally mediated by vagal cardiopulmonary baroreceptors, was absent in animals with neuropathy. It is likely that the vagal nerve fibres to cardiopulmonary baroreceptors as well as the receptors themselves are damaged while shorter carotid sinus nerve fibres are relatively spared in axonal neuropathies. As long as these shorter nerves are intact patients with axonal neuropathy should have relatively normal baroreflexes and normal sympathetic vasomotor tone when measured microneurographically.

The differential effects of prazosin and hydralazine on sympathoadrenal activity in conscious rats

The ability of the vasodilator hydralazine and the α 1-adrenoceptor antagonist prazosin to increase sympathoadrenal outflow was compared by measuring plasma norepinephrine and epinephrine and epinephrine concentrations, norepinephrine clearance and norepinephrine spillover rate into plasma in conscious Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Even though vasodepressor effect of 1 mg/kg (i.p.) of prazosin (−23 mm Hg) was significantly less than that caused by 1 mg/kg (i.p.) of hydralazine (−31 mm Hg) in normotensive rats, the increases in plasma norepinephrine concentration and norepinephrine spillover rate were significantly larger in prazosin-treated rats. In conscious SHR, 0.5 mg/kg (i.p.) of prazosin and 0.3 mg/kg (i.p.) of hydralazine lowered blood pressure to the same extent (−22 mm Hg), but prazosin again produced significantly larger increases in plasma norepinephrine concentration and norepinephrine spillover rate. Neither prazosin nor hydralazine affected norepinephrine clearance, and only prazosin elicited a significant rise in plasma epinephrine concentration. This differential effect of prazosin and hydralazine on sympathoadrenal activity is best explained by the differing effects of these drugs on veneous return and thus the afferent activity of the cardiopulmonary baroreceptors.

Changes in muscle sympathetic nerve activity, venous plasma catecholamines, and calf vascular resistance during mechanical ventilation with PEEP in humans.

The sympathetic reflex response to mechanical ventilation with PEEP was studied in conscious human volunteers (n = 8). Muscle sympathetic nerve activity (MSNA) was measured from the peroneal nerve, calf blood flow, forearm venous plasma catecholamines, blood pressure, heart rate, airway pressure, and end-tidal CO2 (%) during spontaneous breathing and during mechanical ventilation with 0-20 cmH2O PEEP. MSNA increased (P less than 0.01) during PEEP ventilation, from 22 bursts.min-1 at spontaneous breathing to 39 bursts.min-1 at 20 PEEP. This increase in MSNA was accompanied by an increase (P less than 0.01) in calf vascular resistance (CVR) from 35 PRU100 at spontaneous breathing to 48 PRU100 at 15 PEEP with no further increase at 20 PEEP. Venous plasma norepinephrine concentrations increased (P less than 0.01) during PEEP ventilation from 0.19 ng.ml-1 at spontaneous breathing to 0.31 ng.ml-1 at 20 PEEP, whereas plasma epinephrine and dopamine were less than 0.03 ng.ml-1 during the experiment. Blood pressure and heart rate were not affected by PEEP ventilation except at 20 PEEP, where blood pressure and heart rate increased (P less than 0.01). The results show that PEEP ventilation induces a considerable reflex increase of MSNA, reflected also by an increase in CVR and venous plasma norepinephrine. It is proposed that the main mechanism responsible for these reflex adjustments is caused by a decreased activity of the cardiopulmonary low-pressure baroreceptors, in turn resulting from a decrease in cardiac transmural pressures due to PEEP ventilation.

Cardiopulmonary baroreflexes fail to modulate sympathetic responses during isometric exercise in humans: Direct evidence from microneurographic studies

To further evaluate the reported interaction in animals and humans between cardiopulmonary baroreflexes and the somatic pressor reflex, studies were performed in 16 normal men using direct measurements of efferent sympathetic nerve activity to muscle (microneurography) during sustained isometric handgrip (30% maximal voluntary contraction). Forearm vasoconstrictor (plethysmography) and muscle sympathetic nerve activity responses to sustained handgrip were measured during cardiopulmonary baroreceptor deactivation (lower body negative pressure, n = 8) and activation (volume expansion, n = 8). In addition, responses to posthandgrip muscle ischemia were studied during these perturbations of cardiopulmonary baroreflexes.No evidence of an interaction between these two reflex pathways was found. When handgrip was performed during lower body negative pressure, the percent increase in muscle sympathetic nerve activity (+115 ± 17%) was not different fron the sum of the individual sympathetic responses to handgrip and lower body negative pressure performed separately (+106 ± 19%, p = NS). Likewise, the change in forearm vascular resistance (+3.9 ± 0.8 U) for sustained handgrip performed during lower body negative pressure was not different from the algebraic sum of the responses to handgrip and lower body negative pressure when these were performed separately (+4.7 ± 2.7 U, p = NS). No difference was noted in forearm vasoconstrictor and sympathetic nerve activity responses to posthandgrip muscle ischemia and lower body negative pressure when these were performed alone or in combination.Volume expansion also failed to uncover an inhibitory interaction. Handgrip performed before volume expansion resulted in forearm vascular resistance responses (−1.2 ± 0.9 U) that were not different from the responses when such handgrip was performed after volume infusion (+0.9 ± 0.9 U, p = NS). Rather than producing the predicted inhibition of muscle sympathetic nerve activity responses to sustained handgrip, volume infusion actually increased these responses. During prevolume sustained handgrip, the increase in sympathetic nerve activity (+64.5 ± 15.7%) was significantly less than the increase when handgrip was performed after volume infusion (+105.6 ± 20.1%, p < 0.01). A similar lack of inhibitory modulation was seen during posthandgrip muscle ischemia performed before and after volume expansion. These data indicate that the efferent sympathetic responses to the somatic pressor reflex are not modulated by the cardiopulmonary baroreflexes in normal humans.

Depressed baroreflex control of renal nerve activity in conscious WHHL rabbits

The baroreflex control of heart rate and renal nerve activity were examined in conscious Watanabe heritable hyperlipidaemic (WHHL) rabbits. Normal Japanese white rabbits were used as controls. The concentrations of serum cholesterol and triglyceride in WHHL rabbits were ten times higher than those in normal rabbits. The basal values of mean arterial pressure, pulse pressure and heart rate in WHHL rabbits were significantly higher than those in normal rabbits. Baroreceptors were stimulated or unloaded by raising or lowering arterial pressure with injections of phenylephrine or glyceryl trinitrate respectively. The peak changes in heart rate and renal nerve activity were plotted against the peak changes in mean arterial pressure, and a logistic function curve was fitted to the relationships between mean arterial pressure and heart rate, or mean arterial pressure and renal nerve activity. The slopes of both heart rate and renal nerve activity declined in WHHL rabbits. The response of renal nerve activity to acute volume expansion (10 ml.kg-1) with isotonic iso-oncotic dextran was further examined. In the normal rabbit, volume expansion caused renal nerve activity to decrease by 60 +/- 5%, while mean arterial pressure did not change. In the WHHL rabbit the decrease in renal nerve activity caused by volume expansion was significantly attenuated (42 +/- 3%). These results indicate that both sino-aortic and cardiopulmonary baroreceptor mediated changes in renal nerve activity were impaired in the WHHL rabbit.

Fentanyl???Diazepam Anesthesia with or without N2O Does Not Attenuate Cardiopulmonary Baroreflex-Mediated Vasoconstrictor Responses to Controlled Hypovolemia in Humans

Cardiopulmonary baroreceptors located primarily on the low-pressure side of the circulation sense slight reductions in cardiac filling pressures and elicit sustained peripheral vasoconstriction. Because most inhalation and many intravenous anesthetics attenuate arterial baroreflex function, the low-pressure baroreflex may serve a major role in maintaining blood pressure during intraoperative hypovolemia. To activate the low-pressure baroreflex, progressive nonhypotensive reductions in central venous pressure were produced with graded applications of lower body negative pressure (LBNP, -5, -10, -15 mm Hg) in 18 ASA class I patients before elective surgery. This produced linear reductions in stroke volume as determined by impedance cardiography and cardiac output. Cardiopulmonary baroreflex-mediated increases in total and forearm vascular resistance assisted in maintaining stable blood pressure. After ten patients were anesthetized with fentanyl (12.5 micrograms/kg) and diazepam (0.25 mg/kg) and an additional eight received these agents plus supplemental N2O (70%), reflex vasoconstrictor responses to LBNP were not attenuated and, therefore, blood pressure continued to be well maintained despite substantial reductions in cardiac filling pressures. Thus, these anesthetic regimens preserved vasoconstrictor responses mediated by cardiopulmonary baroreflexes. This promoted cardiovascular stability that may be particularly beneficial in patients with cerebral, cardiovascular, or renal disease undergoing surgical procedures with potential for rapid blood loss.