Carotid-cardiac baroreflex function does not influence blood pressure regulation during head-up tilt in humans

The influence of the carotid-cardiac baroreflex on blood pressure regulation was evaluated during supine rest and 40 degrees head-up tilt (HUT) in 9 healthy young subjects with and without full cardiac vagal blockade. The carotid baroreflex responsiveness, or maximal gain (G(MAX)), was assessed from the beat-to-beat changes in heart rate (HR) and mean arterial pressure (MAP) by the variable neck pressure and suction technique ranging in pressure from +40 to -80 Torr, with and without glycopyrrolate (12.0 +/- 1.0 microg/kg body weight; mean +/- SE). In the supine position, glycopyrrolate increased the HR to 91 +/- 3 bpm, from 54 +/- 3; MAP to 89 +/- 2 mmHg, from 76 +/- 2; and cardiac output to 6.8 +/- 0.3 l.min(-1), from 4.9 +/- 0.3 (P < 0.05). The G(MAX) of the carotid baroreflex control of HR was reduced to -0.06 +/- 0.01 bpm.mmHg(-1), from -0.30 +/- 0.02 (P < 0.05) with no significant effect on the G(MAX) of the carotid baroreflex control of MAP. During HUT the carotid baroreflex control of MAP was unchanged, though the G(MAX) of the carotid baroreflex control of HR was increased (P < 0.05). During HUT, central blood volume, assessed by electrical thoracic admittance, and total vascular conductance were decreased with and without glycopyrrolate. Furthermore, glycopyrrolate reduced G(MAX) of the carotid baroreflex control of HR during HUT (P < 0.05) with no significant effect on G(MAX) of the carotid baroreflex control of MAP. These data suggest that during supine rest and HUT-induced decreases in central blood volume, the carotid baroreflex control of HR is mediated primarily via parasympathetic activity. Furthermore, the maintenance of arterial blood pressure during postural stress is primarily mediated by arterial and cardiopulmonary reflex regulation of sympathetic activity and its effects on the systemic vasculature.     

Prone sleeping impairs circulatory control during sleep in healthy term infants: implications for SIDS

STUDY OBJECTIVES: To determine the effects of sleeping position on development of circulatory control in infants over the first 6 months of postnatal age (PNA). DESIGN: Effects of sleeping position, sleep state and PNA on beat-beat heart rate (HR) and mean arterial pressure (MAP) responses to a head-up tilt (HUT) were assessed during sleep in infants at 2-4 wks, 2-3 mo and 5-6 mo PNA. MEASUREMENTS: Daytime polysomnography was performed on 20 full-term infants (12 F/8 M) and MAP was recorded continuously and noninvasively (Finometer). HUTs of 15 degrees were performed during active sleep (AS) and quiet sleep (QS) in both the prone and supine sleeping positions. MAP and HR data were expressed as the percentage change from baseline, and responses were divided into initial, middle and late phases. RESULTS: In the supine position HUT usually resulted in an initial increase (P < 0.05) in HR and MAP, followed by decreases (P < 0.05) in HR and MAP in the middle phase; subsequently HR and MAP returned to baseline in the late phase. By contrast, in the prone position the initial HUT-induced rises in HR and MAP were usually absent, and at 2-3 mo MAP actually decreased (P < 0.05); subsequently HR but not MAP returned to baseline. At 2-3 mo, MAP was lower (P < 0.05) in prone than supine sleeping throughout the HUT. CONCLUSIONS: Prone sleeping alters MAP responses to a HUT during QS at 2-3 mo PNA. Decreased autonomic responsiveness may contribute to the increased risk for SIDS of infants sleeping in the prone position.     

Reliability of orthostatic responses in healthy men aged between 65 and 75 years

The purpose of this study was to investigate the short-, medium- and long-term reproducibility of cardiovascular responses during 90 degrees head-up tilt (HUT) in healthy older men. Twenty-eight healthy male subjects aged 69 (95% confidence intervals, 68-70) years participated in the study. Eight subjects underwent duplicate 90 degrees HUT tests on consecutive days, while 20 subjects underwent four 90 degrees HUT tests performed at baseline, and after 1 week, 1 month and 1 year. Following a 20-min supine resting period, each subject was rapidly tilted to the upright vertical position (90 degrees HUT) and remained in that position for 15 min. Beat-by-beat recordings of mean (MAP), systolic (SBP) and diastolic (DBP) pressures were made via Finapres, while heart rate (HR) was monitored continuously from an electrocardiogram. No significant test-retest differences (P > 0.05) were observed for the changes in HR, MAP, SBP or DBP during 90 degrees HUT. These measurements demonstrated high reproducibility (intraclass correlation coefficient, r = 0.91-0.99, P < 0.05). The supine resting and tilted HR, MAP, SBP and DBP over the 1-week, 1-month and 1-year period were not significantly different (P > 0.05) from baseline, and demonstrated high reproducibility (intraclass correlation coefficient, r = 0.82-0.98, P < 0.05). The results of this study demonstrate that in healthy older men, cardiovascular responses during orthostasis are highly reproducible, and this reproducibility is maintained over a 12-month period. These findings demonstrate that the 90 degrees HUT test offers a reproducible method of monitoring longitudinal orthostatic responses in healthy older men.     

Norepinephrine and epinephrine responses during orthostatic intolerance in healthy elderly men

In young individuals, orthostatic intolerance is associated with marked increases in plasma epinephrine (EPI) concentrations and attenuated rises in plasma norepinephrine (NE) concentrations. This study investigated the cardiovascular, EPI and NE responses of healthy elderly males during orthostatic stress. Twelve men (68 +/- 1 yr) with a recent history of orthostatic hypotension and who exhibited orthostatic intolerance (HYPO) during 90 degrees head-up tilt (HUT) were compared with 12 men (69 +/- 1 yr) without a history of orthostatic hypotension and who remained normotensive (NORMO) throughout 90 degrees HUT. Beat-by-beat recordings of heart rate (HR), mean (MAP), systolic (SBP), diastolic (DBP), and pulse (PP) pressures were made throughout 90 degrees HUT. Blood samples obtained during supine rest and 90 degrees HUT were analyzed for changes in EPI and NE concentrations, hematocrit, hemoglobin and plasma volume. Compared to supine rest, orthostatic intolerance was characterized by significant reductions (p < 0.0001) in MAP, SBP, DBP, and PP. The HR, MAP, SBP, DBP, and PP at the termination of 90 degrees HUT was significantly lower (p < 0.0001) for HYPO than NORMO. The 90 degrees HUT position resulted in significant increases (p < 0.01) in NE for both HYPO and NORMO, with the rise in NE significantly lower (p < 0.05) in HYPO. There were no differences between groups regarding EPI concentrations at the termination of 90 degrees HUT. These results suggest that the magnitude of arterial pressure (AP) reduction does not influence the EPI response during orthostasis in healthy elderly men. However, marked reductions in AP, leading to orthostatic intolerance, are associated with inadequate increases in NE in these individuals.     

Involvement of the paraventricular nucleus (PVN) of hypothalamus in the cardiovascular alterations to head up tilt in conscious rats

We evaluated the involvement of paraventricular nucleus (PVN) in the changes in mean arterial pressure (MAP) and heart rate (HR) during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to PVN and artery and vein catheters were submitted to MAP and HR recording in conscious state and induction of HUT. The HUT induced an increase in MAP and HR and the pretreatment with prazosin and atenolol blocked these effects. After inhibition of neurotransmission with cobalt chloride (1 mM/100 nl) into the PVN the HR parameters did not change, however we observed a decrease in MAP during HUT. Our data suggest the involvement of PVN in the brain circuitry involved in cardiovascular adjustment during orthostatic challenges.     

Decreased tolerance to orthostatic stress in diabetics

Cardiovascular responses to head up tilt (HUT) were investigated in chronic diabetics (having disease of 8 to 10 years duration) and in control subjects. The parameters recorded were heart rate (HR), blood pressure (BP), forearm blood flow (FABF) and forearm vascular resistance (FAVR). Recordings were made first in the supine position, next after HUT, and thirdly in the recovery period after return to the supine position. Normal subjects responded to HUT by a marked increase in HR (P less than 0.001), decrease in FABP (P less than 0.001) and increase in FAVR (P less than 0.001). The diastolic blood pressure (DBP) and mean blood pressure (MBP) showed appreciable increase (P less than 0.001, P less than 0.01 respectively) without significant fall in systolic blood pressure (SBP). The maximum alteration in cardiovascular responses was observed immediately after HUT (within 15 sec). The cardiovascular responses to HUT in diabetics were found to be significantly impaired compared to control subjects. The impairment of cardiovascular responses in diabetics in indicative of autonomic neuropathy which can be detected by these tests before the development of clinical signs of the neuropathy.     

Sympathetic influence on cardiovascular responses to sustained head-up tilt in humans

Sympathetic β-adrenergic influences on cardiovascular responses to 50d? head-up tilt were evaluated with metoprolol (β₁-blockade; 0.29 mg kg^-1) and propranolol (β₁ and β-₂-blockade; 0.28 mg kg^-1) in eight males. A normotensive-tachycardic phase was followed by a hypotensive-bradycardic episode associated with presyncopal symptoms after 23pL3 min (control, mean pLSE). Head-up tilt made thoracic electrical impedance (3.0pL10Ω), mean arterial pressure (MAP, 86pL4-93pL4 mmHg), heart rate (HR, 63pL3-99pL10 beats min^-1) and total peripheral resistance (TPR, 15pL1-28pL4 mmHg min L^-1) increase, while central venous oxygen saturation (74pL2-58pL4%), cardiac output (5.7pL0.1–3.1pL0.3 L min^-1), stroke volume (95pL6-41pL5 mL) and pulse pressure (55pL4-49pL4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7pL2-0pL1 mmHg), but it remained stable during the sustained tilt. At the appearance of preswyncopal symptoms MAP (49pL3 mmHg), HR (66pL4 beats min^-1) and TPR (15pL3 mmHg min L^-1) decreased (P < 0.05). Neither metoprolol or propranolo changed tilt tolerance or cardiovascular variables, except for HR that remained at 57pL2 (metoprolol) and 55pL3 beats min^-1 (propranolol), and MAP that remained at 87pL5 mmHg during the first phase with metoprolol. In conclusion, sympathetic activation was crucial for the heart rate elevation during normotensive head-up tilt, but not for tilt tolerance or for the associated hypotension and bradycardia.     

Modulation of plasma adrenomedullin by epinephrine infusion during head up tilt

We investigated whether head up tilt (HUT) with and without simultaneous epinephrine infusion modulate plasma adrenomedullin. We studied eight healthy male volunteers, using two 5 min 70° HUT trials: control (saline infusion) and intervention (epinephrine infusion, titrated to a dose which increased supine systolic pressure by 20% above resting values). Protocols were randomized and separated by 2 weeks. Cardiac function and systolic time intervals, recorded using a phonocardiograph microphone, included left ventricular ejection time (LVET), pre-ejection period (PEP), PEP/LVET and electromechanical systole (QS2). Compared to saline infusion, epinephrine increased supine adrenomedullin (3.2 ± 0.8 pmol/l, i.e., mean ± SEM, respectively), heart rate (HR) (+11.3 ± 2.6 bpm), systolic pressure (+18.4 ± 2.6 mmHg) but decreased supine LVET, LVET corrected for HR (LVETi) and QS2-time (all p = 0.004). Despite similar HUT induced thoracic fluid shifts, reflected by similar thoracic impedance changes, HUT-induced adrenomedullin increases were minimal in epinephrine-supplemented men in comparison to controls (+8% vs. 42%). During HUT, epinephrine infusion decreased only the LVET (p = 0.039). Our findings confirm that short-term HUT increases plasma adrenomedullin. They further suggest that with increased supine epinephrine levels (epinephrine infusion clamping systolic arterial pressure at 120% control level), supine cardiac performance rises to a level similar to that during HUT, while adrenomedullin is still elevated with HUT. This might be in accordance with a ‘dampening’ role of adrenomedullin during catecholaminergic cardiovascular stimulation. As epinephrine is used as a drug to treat cardiac arrest and ventricular arrhythmias, our results may have important clinical/emergency resuscitation applications.     

Blood pressure and heart rate responses to mental stress in spontaneously hypertensive (SHR) and normotensive (WKY) rats on various sodium diets

Normotensive (WKY) and hypertensive rats (SHR) were, from 5 to 12 weeks of age, given ‘low’ (LNa), ‘control’ and ‘high’ (HNa) Na diets (0.5, 5 and 50 mmol-100 g^-1 food, respectively, during weekly recordings of body weight, conscious indirect systolic blood pressure (SBP) and heart rate (HR). During the last week, mean arterial pressure (MAP) and HR responses to standardized stress stimuli (air jet) were recorded before and after sequential cardiac nerve blockade. While resting, SBP was about equal in all WKY groups, but it was significantly reduced in SHR-LNa (152 mmHg versus 174 and 178 mmHg in SHR controls and HNa; P < 0.05). In both LNa groups HR was elevated nearly 25% compared with controls, being in SHR 513 versus 419 bpm (P < 0.01) and in WKY 489 versus 393 bpm (P < 0.01). Cardiac nerve blockade indicated that this HR elevation was about equally due to elevations of sympathetic activity and ‘intrinsic’ pacemaker activity. SHR-LNa also showed attenuated MAP elevations to acute mental stress. There were, however, no significant differences between groups concerning haematocrit or plasma Na-K levels. The results suggest that SHR have a greater salt requirement than WKY, as Na restriction to one-tenth of normal led to a considerable MAP reduction in SHR despite compensatory sympathetic activation, and also to attenuated pressor responses to mental stress. Further, the cardiovascular effects in SHR were much more extensive when on a low-Na diet than when Na intake was increased tenfold above normal.     

Modulation of extracellular glutamate and pressor response to muscle contraction during NMDA-receptor blockade in the rostral ventrolateral medulla

Recently our laboratory demonstrated increases in extracellular glutamate concentrations within the rostral ventrolateral medulla (RVLM) during static muscle contraction (Caringi, D.C., Maher, T., Chaiyakul, P., Asmundsson, G., Ishide, T., Ally, A. Pflügers Arch. Eur. J. Physiol., 435:465-471, 1998). In this study, we determined effects of microdialyzing D(-)2-amino-7-phosphonohepatanoic acid (AP-7), an NMDA-receptor antagonist, into the RVLM on changes in mean arterial pressure (MAP), heart rate (HR), and extracellular glutamate levels during muscle contraction in anesthetized rats. Bilateral placements of microdialysis probes into the RVLM were verified by perfusing L-glutamate and obtaining a pressor response. Muscle contraction for 2 min, increased MAP and HR by 22+/-4 mmHg and 28+/-5 bpm, respectively. Extracellular glutamate as determined by microdialysis increased from 0.8+/-0.2 to 6.3+/-1.2 ng/5 microl. Microdialysis of AP-7 (1.0 microM) for 30 min inhibited contraction-evoked MAP and HR responses (10+/-3 mmHg and 13+/-3 bpm) and attenuated increases in glutamate during muscle contraction. Developed tensions did not differ during contractions before and after AP-7. Results demonstrate that NMDA-receptor blockade in the RVLM inhibits cardiovascular responses during static muscle contraction via a reduction in extracellular glutamate levels.     

Reduced orthostatic tolerance following 4 h head-down tilt

Summary The cardiovascular responses to a 10-min 1.22 rad (70°) head-up tilt orthostatic tolerance test (OST) was observed in eight healthy men following each of a 5-min supine baseline (control), 4 h of 0.1 rad (6°) head-down tilt (HDT), or 4 h 0.52 rad (30°) headup tilt (HUT). An important clinical observation was presyncopal symptoms in six of eight subjects following 4 h HDT, but in no subjects following 4 h HUT. Immediately prior to the OST, there were no differences in heart rate, stroke volume, cardiac output, mean arterial pressure and total peripheral resistance for HDT and HUT. However, stroke volume and cardiac output were greater for the control group. Mean arterial pressure for the control group was less than HDT but not HUT. Over the full 10-min period of OST, the mean arterial pressure was not different between groups. Heart rate increased to the same level for all three treatments. Stroke volume decreased across the full time period for control and HDT, but only at 3 and 9 min for HUT. There was a higher total peripheral resistance in the HDT group than control or HUT. The pre-ejection period to left ventricular ejection time ratio was less in HDT than for control or HUT groups. These data indicate a rapid adaptation of the cardiovascular system to 4 h HDT that appears to be inappropriate on reapplication of a head to foot gravity vector. We speculate that the cause of the impaired orthostatic tolerance is decreased tone in venous capacitance vessels so that venous return is inadequate.     

Leg vascular resistance increases during head-up tilt in paraplegics

Despite loss of centrally mediated sympathetic vasoconstriction to the legs, spinal cord-injured individuals cope surprisingly well with an orthostatic challenge. This study assessed changes in leg vascular resistance following head-up tilt in healthy (C) and in paraplegic (P) individuals. After 10 min of supine rest, subjects were tilted 30° head-up. Mean arterial pressure (MAP) and total peripheral resistance (TPR) increased in C (MAP from 76.7±6.6 mmHg to 80.6±8.2 mmHg; TPR from 1.12±0.26 AU to 1.19±0.31 AU) while both remained unchanged in P. Echo Doppler ultrasound determined red blood cell velocity in the femoral artery, which decreased (P from 18.9±6.2 cm/s to 12.5±4.5 cm/s, P=0.001; C from 16.3±6.2 cm/s to 10.8±5.0 cm/s, P=0.001) and leg vascular resistance, which increased (P from 402±137 AU to 643±274 AU, P=0.001; C from 238±68 AU to 400±122 AU, P=0.003) from supine to upright. The present study shows that independent of supraspinal sympathetic control, humans are able to increase leg vascular resistance and maintain blood pressure during head-up tilt.     

Sympathetic responses to Valsalva's manoeuvre following bed rest.

The purpose of this study was to examine whether 14 days of head-down tilt bed rest (HDBR) alters autonomic regulation during Valsalva's manoeuvre (VM) and if this would predict blood pressure control during a 60 degrees head-up tilt (HUT) test. To examine autonomic control of blood pressure, we measured the changes in systolic (delta SBP) and diastolic (delta DBP) blood pressure between baseline and the early straining (Phase IIE) period of VM (20 sec straining to 40 mmHg; N = 7) in conjunction with changes in muscle sympathetic nerve activity (MSNA; microneurography) burst frequency (B/min) and total activity (% delta) from baseline over the 20-sec straining period. MSNA data were successfully recorded from 6 of the 7 individuals. The averaged responses from three repeated VMs performed in the supine position were compared between the pre- and post-HDBR tests. Compared with the pre-HDBR test, a greater reduction in SBP, DBP, and MAP was observed during Phase IIE following HDBR, p < 0.05. The increase in MSNA burst frequency during straining was augmented in the post- compared with the pre-HDBR test, p < 0.0001, as was the Phase IV blood pressure overshoot, p < 0.05. Although all subjects completed the 20-min pre-HDBR tilt test without evidence of hypotension or orthostatic intolerance, the post-HDBR test was stopped early in 5 of the 7 subjects due to systolic hypotension. The responses during the VM suggest that acute autonomic adjustments to rapid blood pressure changes are preserved after bed rest. Furthermore, MSNA and blood pressure responses during VM did not predict blood pressure control during orthostasis following HDBR.     

Effects of inspiratory impedance on hemodynamic responses to a squat–stand test in human volunteers: implications for treatment of orthostatic hypotension

Recent studies in our laboratory demonstrated that spontaneous breathing through an inspiratory impedance threshold device (ITD) increased heart rate (HR), stroke volume (SV), cardiac output (Q), and mean arterial blood pressure (MAP) in supine human subjects. In this study, we tested the effectiveness of an ITD as a countermeasure against development of orthostatic hypotension, provoked using a squat-to-stand test (SST). Using a prospective, randomized blinded protocol, 18 healthy, normotensive volunteers (9 males, 9 females) completed two-counterbalanced 6-min SST protocols with and without (sham) an ITD set to open at 0.7 kPa (7-cm H₂O) pressure. HR, SV, Q, total peripheral resistance (TPR), and MAP were assessed noninvasively with infrared finger photoplethysmography. Symptoms were recorded on a 5-point scale (1=normal; 5=faint) of subject perceived rating (SPR). The reduction in TPR produced by SST (–35±5 %) was not affected by the ITD. Reduction in MAP with ITD during the transient phase of the SST (–3.6±0.5 kPa or –27±4 mmHg) was less (P=0.03) than that measured while breathing through a sham device (–4.8±0.4 kPa or –36±3 mmHg) despite similar (P<0.926) elevations in HR of 15±2 bpm. SV (+2±4 %) and Q (+22±5 %) with the ITD were higher (P<0.04) than SV (–8±4 %) and Q (+10±6 %) without the ITD. SPR was 1.4±0.1 with ITD compared to 2.0±0.2 with the sham device (P<0.04). This reduction in orthostatic symptoms with application of an ITD during the SST was associated with higher MAP, SV and Q. Our results demonstrate the potential application of an ITD as a countermeasure against orthostatic hypotension.     

Reproducibility of the alterations in circulation and cerebral oxygenation from supine rest to head-up tilt.

Cardiovascular stability, as affected by several diseases, may be assessed by head-up tilt testing. Follow-up studies are essential in both evaluating interventions and assessing progression. However, data on the reproducibility of the changes in circulatory status and cerebral oxygenation provoked by head-up tilt testing are fundamental to follow-up studies. The aim of this study was, therefore, to assess the reproducibility of the alterations in stroke volume (SV), mean arterial pressure (MAP), as well as oxygenated ([O2Hb]) and deoxygenated haemoglobin ([HHb]) concentration in cerebral tissue from supine rest (SUP) to head-up tilt (HUT). SV was calculated by Modelflow, a pulse contour method, from the finger arterial pressure wave measured by Portapres, the portable version of Finapres. [O2Hb] and [HHb] were measured using near-infrared spectroscopy (NIRS). Ten healthy individuals visited the laboratory on two different days. On both days, they underwent 10 min SUP followed by 10 min 70 degrees HUT twice. SV decreased, which was (in part) compensated for by an increased heart rate, while MAP increased slightly during HUT compared with SUP. Although [HHb] increased during HUT, no presyncope symptoms were experienced. The circulatory variables (SV, HR and MAP) as well as [HHb] showed an acceptably small systematic and random error as well as reproducibility error compared with the observed difference between HUT and SUP and were similar between and within visits. Therefore, it is concluded that MAP measured by Portapres and SV calculated by Modelflow as well as HHb measured by NIRS seem to be reproducible and may therefore be used in follow-up studies.     

Haemodynamic and baroreflex responses to whole-body tilting in exercising men before and after 6 weeks of bedrest

We sought to determine whether the cardiovascular deconditioning that occurs in exercising men after prolonged (42 days) bedrest in the head-down tilt (HDT) position is primarily related to mechanical changes in the heart or to an impaired arterial-cardiac-chronotropic baroreflex. Seven subjects were studied before (C, control) and repeatedly after HDT with rapid tilting between the upright and supine positions during steady-state 50-W dynamic leg exercise. Ventricular interdependence was assumed to be an index of cardiac size; it was assessed on the basis of the initial dip of arterial pulse pressure (PP) induced by a sudden tilt from the upright to the supine position (down-tilt). Arterial-cardiac-chronotropic baroreflex sensitivity (ABS) was assessed as the ratio between tilt-induced heart rate transients and the preceding (and reciprocal) transient in arterial pressure. On the first day of recovery, the initial PP dip was −4 (2) mmHg (where 1 mmHg is 0.13 kPa), less than half of the control value; on subsequent recovery days, the initial PP dip was not significantly different from the control value. When tilting from the upright to the supine position, mean ABS ranged from 1.02 to 1.06 bpm/mmHg during three separate control sessions. Tilts in the opposite direction gave lower ABS values because of the more sluggish HR response and ranged from 0.43 to 0.45 bpm/mmHg in the control situations. ABS did not change after HDT. Our results indicate that impairments of the cardiovascular system after long-term bedrest are of haemodynamic rather than baroreflex origin. Accepted: 8 March 2000     

Autonomic cardiovascular response to acute hypoxia and passive head-up tilting in humans

Acute hypoxia may alter autonomic cardiovascular reflexes during orthostasis. Heart rate variability (HRV), arterial blood pressure (MAP), and respiratory sinus arrhythmia (RSA) were recorded during supine (SUP) and passive head up tilt (HUT) in eight healthy humans, spontaneously breathing either room air or 10 % O₂ in N₂. In the time domain, heart rate increased and variability decreased with HUT in both trials, with no difference between trials. In the frequency domain, normalized low frequency HRV increased, and normalized high frequency HRV decreased with HUT in both trials, with no difference between trials. MAP was 74.9 (8.6) and 77.5 (11.7) mmHg when SUP in the room air and hypoxia trials, respectively. A significant increase in MAP occurred with HUT in the room air trial but not in the hypoxia trial. In both trials, end tidal CO₂ decreased with HUT, with no difference between trials. In the room air trial, end tidal O₂ increased with HUT, whereas during the hypoxia trial, end tidal O₂ decreased with HUT. The distribution of heart beats relative to the phase of ventilation (%HB_IN and %HB_OUT) was similar in both trials: the %HB_IN was 43.5 (3.3) % and %HB_OUT was 56.5 (4.2) % breathing room air when SUP, and 45.5 (3.0) and 54.5 (3.2) when hypoxic and SUP. For both trials, this distribution did not change with HUT. As both HRV and RSA showed similar responses to HUT when spontaneously breathing either room air or 10 % O₂ in N₂, we suggest that autonomic cardiovascular reflexes are preserved during acute hypoxia.     

Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans

Effects of the GABAergic drug diazepam (0.15 mg kg^-1, i.v.) on cardiovascular and endocrine responses to 50± head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1, 10) = 6.45; P < 0.03). After 42 ± 4 min of sustained tilt with saline (control) and 47 ± 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2–3-fold increase in plasma ACTH, β-endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance.     

Effects of opioid receptor activation on cardiovascular responses and extracellular monoamines within the rostral ventrolateral medulla during static contraction of skeletal muscle.

During static muscle contraction, activation of opioid receptors alters the extracellular glutamate concentrations within the rostral ventrolateral medulla (RVLM). In addition, microdialysis of glutamate in the ventrolateral medulla (VLM) increases the release of norepinephrine (NE), dopamine (DA), and serotonin (5-HT). Therefore, we hypothesized that extracellular concentrations of these monoamines as well as cardiovascular responses during static skeletal muscle contraction would be modulated following administration of [D-Ala(2)]methionine enkephalinamide (DAME), an opioid receptor agonist, into the RVLM. Microdialysis of 100 microM DAME into the RVLM of 10 rats significantly (P<0.01) decreased extracellular levels (in pg/10 microl) of NE (from 3.3+/-0.3 to 1.9+/-0.3), DA (from 5.5+/-0.2 to 3.7+/-0.3), and 5-HT (from 6.1+/-0.8 to 3.6+/-0.2) during static exercise. After microdialysis of DAME, the exercise pressor reflex also significantly (P<0.01) decreased mean arterial pressure (MAP) by 13+/-3 mmHg and heart rate (HR) by 16+/-6 bpm, compared with control (MAP=22+/-4 mmHg and HR=31+/-7 bpm). Subsequently, after 30 min microdialysis of naloxone, an opioid receptor antagonist, muscle contraction increased the extracellular monoamine levels (in pg/10 microl, 3.8+/-0.3 NE; 5.2+/-0.3 DA; and 5.5+/-0.4 5-HT) similar to the control groups and evoked a reversal of cardiovascular responses. Similarly, 30 min of microdialyzing naloxone, added to the perfusing medium containing DAME, reversed the attenuating effects of DAME on monoamines, MAP, and HR during a muscle contraction. Furthermore, microdialysis of 100 microM naloxone alone for 30 min potentiated cardiovascular responses and monoamine levels during a muscle contraction. In summary, the present data demonstrates that microdialysis of DAME into RVLM attenuates the exercise pressor reflex mediated increases in MAP, HR and extracellular levels of biogenic monoamines. A subsequent microdialysis of naloxone reversed the effects suggesting that an opioidergic mechanism within RVLM modulates the exercise pressor reflex. Overall, the present study provides further insights into the opioidergic modulation of the exercise pressor reflex.     

Perinatal MSG treatment attenuates fasting-induced bradycardia and metabolic suppression

We studied the effect of arcuate nucleus (ARC) lesions induced pharmacologically by the perinatal treatment of monosodium l-glutamate (MSG) on the cardiovascular, metabolic, and behavioral responses to fasting. Saline and MSG-treated male Sprague-Dawley rats were instrumented with telemetry devices for measurement of mean arterial pressure (MAP) and heart rate (HR) and housed in room calorimeters at an ambient temperature (T(a)) of 23 degrees C for assessment of oxygen consumption (VO(2)). At baseline, controls and MSG-treated rats had similar MAP (control=95+/-4; MSG=91+/-2 mmHg), HR (control=323+/-4; MSG=324+/-2 bpm), and VO(2) (control=8.7+/-0.3; MSG=8.6+/-0.2 ml/min). There were no differences in fasting-induced reductions in body weight or in food intake upon refeeding. MSG-treatment significantly attenuated fasting-induced reductions in HR and VO(2). This effect was specific to reduced caloric availability, as MSG-treated rats exhibited intact capacity to both increase and decrease HR and VO(2) in response to cold (T(a)=15 degrees C) and to thermoneutrality (T(a)=30 degrees C). Additional studies were performed in saline- and MSG-treated rats chronically treated with beta(1)-adrenergic receptor blockade (atenolol) prior to and during fasting. In controls, the cardiovascular responses to fasting during beta(1)-blockade were blunted and generally mimicked the effects of MSG-treatment, while beta(1)-blockade had no additional effect on MSG-treated rats. The results are consistent with the hypothesis that ARC neuronal signaling is requisite for intact homeostatic responses to fasting and may participate in fasting-induced withdrawal of cardiac sympathetic activity.