Modulation of the spontaneous beat-to-beat fluctuations in peripheral vascular resistance during activation of muscle metaboreflex

Continuous measurement of leg blood flow (LBF) using Doppler ultrasound with simultaneous noninvasive mean arterial blood pressure (MAP) measurement permits beat-to-beat estimates of leg vascular resistance (LVR) in humans. We tested the hypothesis that the beat-to-beat fluctuations in LVR and the dynamic relationship between MAP and LVR are modulated by the activation of muscle metaboreflex. Twelve healthy subjects performed a 1-min isometric handgrip exercise at 50% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). We then employed transfer function analysis to examine the dynamic relationships between MAP and LBF and between MAP and LVR, both at rest (control) and during PEMI. We found the following. 1) The spectral power for LBF and LVR in low-frequency ( approximately 0.03-0.15 Hz) range significantly increased from control during PEMI without a significant change in the high-frequency ( approximately 0.15-0.35 Hz) power. 2) During PEMI, the transfer function gains for MAP-LBF and MAP-LVR relationships in the low-frequency ( approximately 0.05-0.15 Hz) range were significantly increased during PEMI (vs. control) but were unchanged in the high-frequency ( approximately 0.2-0.3 Hz) range. 3) The phases for MAP-LBF and MAP-LVR relationships were not different during control and PEMI. The phase for MAP-LVR relationship revealed that changes in MAP were followed by directionally similar changes in LVR, which is consistent with the characteristics of intrinsic vascular regulatory mechanisms such as the myogenic response of the resistance arteries. We suggest that, in humans, modulation of the dynamic MAP-LVR relationship during activation of the muscle metaboreflex reflects complex interactions between intrinsic vascular regulatory mechanisms and sympathetic vascular regulation.     

Effect of muscle metaboreflex activation on carotid-cardiac baroreflex function in humans

Whether the activation of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) influences cardiac baroreflex responsiveness remains incompletely understood. A potential explanation for contrasting findings of previous reports may be related to differences in the magnitude of muscle metaboreflex activation utilized. Therefore, the present study was designed to investigate the influence of graded intensities of muscle metaboreflex activation on cardiac baroreflex function. In eight healthy subjects (24 +/- 1 yr), the graded isolation of the muscle metaboreflex was achieved by post-exercise ischemia (PEI) following moderate- (PEI-M) and high- (PEI-H) intensity isometric handgrip performed at 35% and 45% maximum voluntary contraction, respectively. Beat-to-beat heart rate (HR) and blood pressure were measured continuously. Rapid pulse trains of neck pressure and neck suction (+40 to -80 Torr) were applied to derive carotid baroreflex stimulus-response curves. Mean blood pressure increased significantly from rest during PEI-M (+13 +/- 3 mmHg) and was further augmented during PEI-H (+26 +/- 4 mmHg), indicating graded metaboreflex activation. However, the operating point gain and maximal gain (-0.51 +/- 0.09, -0.48 +/- 0.13, and -0.49 +/- 0.12 beats.min(-1).mmHg(-1) for rest; PEI-M and PEI-H) of the carotid-cardiac baroreflex function curve were unchanged from rest during PEI-M and PEI-H (P > 0.05 vs. rest). Furthermore, the carotid-cardiac baroreflex function curve was progressively reset rightward from rest to PEI-M to PEI-H, with no upward resetting. These findings suggest that the muscle metaboreflex contributes to the resetting of the carotid baroreflex control of HR; however, it would appear not to influence carotid-cardiac baroreflex responsiveness in humans, even with high-intensity activation during PEI.     

Effect of active muscle mass during ischemic exercise on peak lower leg vascular conductance.

Uncertainty exists as to whether a period of passive arterial occlusion (PAO) or ischemic exercise (IE) results in peak lower leg vascular conductance (LVC). This uncertainty is due to the different body positions, active muscle mass, and occlusion times used for PAO or IE. The purpose of this study was to examine whether 10 min of PAO elicits a similar LVC compared with ischemic dorsiflexion (IDF), ischemic plantar flexion (IPF), and ischemic plantar-dorsiflexion (IPDF). Ten subjects (5 women, 27 +/- 9 yr, 68 +/- 3 kg) were studied on 3 days over 1 wk in a semireclined position with the right foot attached to an isokinetic dynamometer. Mean arterial pressure (Finapres) and lower leg blood flow (LBF, venous occlusion plethysmography) were measured at rest and after PAO and IE. PAO was administered randomly on 1 of the 3 days and before IE. IE protocols consisted of maximal isokinetic dorsiflexion and/or plantar flexion at 120 and 60 degrees/s, respectively. In a second experiment, an additional eight subjects (4 women, 29 +/- 12 yr, 77 +/- 12 kg) were studied to examine the effect of isokinetic speed during IDF on peak LBF and LVC. Peak LVC (ml.min(-1).100 ml(-1).mmHg(-1)) was similar among IPF (0.590 +/- 0.16), IPDF (0.532 +/- 0.17), and PAO (0.511 +/- 0.18), and significantly lower after IDF (0.334 +/- 0.15). No differences in peak LBF and LVC were observed after IDF using different isokinetic speeds. We conclude that 10 min of PAO, IPF, and IPDF performed in a similar posture are adequate stimuli to elicit peak LVC.     

Carotid baroreflex control of leg vascular conductance at rest and during exercise.

We sought to test the hypothesis that the carotid baroreflex (CBR) alters mean leg blood flow (LBF) and leg vascular conductance (LVC) at rest and during exercise. In seven men and one woman, 25 +/- 2 (SE) yr of age, CBR control of LBF and LVC was determined at rest and during steady-state one-legged knee extension exercise at approximately 65% peak O(2) uptake. The application of 5-s pulses of +40 Torr neck pressure and -60 Torr neck suction significantly altered mean arterial pressure (MAP) and LVC both at rest and during exercise. CBR-mediated changes in MAP were similar between rest and exercise (P > 0.05). However, CBR-mediated decreases in LVC (%change) to neck pressure were attenuated in the exercising leg (16.4 +/- 1.6%) compared with rest (33 +/- 2.1%) and the nonexercising leg (23.7 +/- 1.9%) (P < 0.01). These data suggest CBR control of blood pressure is partially mediated by changes in leg vascular tone both at rest and during exercise. Furthermore, despite alterations in CBR-induced changes in LVC during exercise, CBR control of blood pressure was well maintained.     

Muscle metaboreflex control of coronary blood flow

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF) and vascular conductance (CVC) in conscious, chronically instrumented dogs during treadmill exercise ranging from mild to severe workloads. Metaboreflex responses were also observed during mild exercise with constant heart rate (HR) of 225 beats/min and beta(1)-adrenergic receptor blockade to attenuate the substantial reflex increases in cardiac work. The muscle metaboreflex was activated via graded partial occlusion of hindlimb blood flow. During mild exercise, with muscle metaboreflex activation, hindlimb ischemia elicited significant reflex increases in mean arterial pressure (MAP), HR, and cardiac output (CO) (+39.0 +/- 5.2 mmHg, +29.9 +/- 7.7 beats/min, and +2.0 +/- 0.4 l/min, respectively; all changes, P < 0.05). CBF increased from 51.9 +/- 4.3 to 88.5 +/- 6.6 ml/min, (P < 0.05), whereas no significant change in CVC occurred (0.56 +/- 0.06 vs. 0.59 +/- 0.05 ml. min(-1). mmHg(-1); P > 0.05). Similar responses were observed during moderate exercise. In contrast, with metaboreflex activation during severe exercise, no further increases in CO or HR occurred, the increases in MAP and CBF were attenuated, and a significant reduction in CVC was observed (1.00 +/- 0.12 vs. 0.90 +/- 0.13 ml. min(-1). mmHg(-1); P < 0.05). Similarly, when the metaboreflex was activated during mild exercise with the rise in cardiac work lessened (via constant HR and beta(1)-blockade), no increase in CO occurred, the MAP and CBF responses were attenuated (+15.6 +/- 4.5 mmHg, +8.3 +/- 2 ml/min), and CVC significantly decreased from 0.63 +/- 0.11 to 0.53 +/- 0.10 ml. min(-1). mmHg(-1). We conclude that the muscle metaboreflex induced increases in sympathetic nerve activity to the heart functionally vasoconstricts the coronary vasculature.     

Vestibulosympathetic reflex during the early follicular and midluteal phases of the menstrual cycle

Evidence suggests that both the arterial baroreflex and vestibulosympathetic reflex contribute to blood pressure regulation, and both autonomic reflexes integrate centrally in the medulla cardiovascular center. A previous report indicated increased sympathetic baroreflex sensitivity during the midluteal (ML) phase of the menstrual cycle compared with the early follicular (EF) phase. On the basis of this finding, we hypothesize an augmented vestibulosympathetic reflex during the ML phase of the menstrual cycle. Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate responses to head-down rotation (HDR) were measured in 10 healthy females during the EF and ML phases of the menstrual cycle. Plasma estradiol (Delta72 +/- 13 pg/ml, P < 0.01) and progesterone (Delta8 +/- 2 ng/ml, P < 0.01) were significantly greater during the ML phase compared with the EF phase. The menstrual cycle did not alter resting MSNA, MAP, and heart rate (EF: 13 +/- 3 bursts/min, 80 +/- 2 mmHg, 65 +/- 2 beats/min vs. ML: 14 +/- 3 bursts/min, 81 +/- 3 mmHg, 64 +/- 3 beats/min). During the EF phase, HDR increased MSNA (Delta3 +/- 1 bursts/min, P < 0.02) but did not change MAP or heart rate (Delta0 +/- 1 mmHg and Delta1 +/- 1 beats/min). During the ML phase, HDR increased both MSNA and MAP (Delta4 +/- 1 bursts/min and Delta3 +/- 1 mmHg, P < 0.04) with no change in heart rate (Delta0 +/- 1 beats/min). MSNA and heart rate responses to HDR were not different between the EF and ML phases, but MAP responses to HDR were augmented during the ML phase (P < 0.03). Our results demonstrate that the menstrual cycle does not influence the vestibulosympathetic reflex but appears to alter MAP responses to HDR during the ML phase.     

Spontaneous baroreflex control of cardiac output during dynamic exercise, muscle metaboreflex activation, and heart failure

We have previously shown that spontaneous baroreflex-induced changes in heart rate (HR) do not always translate into changes in cardiac output (CO) at rest. We have also shown that heart failure (HF) decreases this linkage between changes in HR and CO. Whether dynamic exercise and muscle metaboreflex activation (via imposed reductions in hindlimb blood flow) further alter this translation in normal and HF conditions is unknown. We examined these questions using conscious, chronically instrumented dogs before and after pacing-induced HF during mild and moderate dynamic exercise with and without muscle metaboreflex activation. We measured left ventricular systolic pressure (LVSP), CO, and HR and analyzed the spontaneous HR-LVSP and CO-LVSP relationships. In normal animals, mild exercise significantly decreased HR-LVSP (-3.08 +/- 0.5 vs. -5.14 +/- 0.6 beats.min(-1).mmHg(-1); P < 0.05) and CO-LVSP (-134.74 +/- 24.5 vs. -208.6 +/- 22.2 ml.min(-1).mmHg(-1); P < 0.05). Moderate exercise further decreased both and, in addition, significantly reduced HR-CO translation (25.9 +/- 2.8% vs. 52.3 +/- 4.2%; P < 0.05). Muscle metaboreflex activation at both workloads decreased HR-LVSP, whereas it had no significant effect on CO-LVSP and the HR-CO translation. HF significantly decreased HR-LVSP, CO-LVSP, and the HR-CO translation in all situations. We conclude that spontaneous baroreflex HR responses do not always cause changes in CO during exercise. Moreover, muscle metaboreflex activation during mild and moderate dynamic exercise reduces this coupling. In addition, in HF the HR-CO translation also significantly decreases during both workloads and decreases even further with muscle metaboreflex activation.     

Systemic hemodynamic and regional blood flow changes in response to chronic reductions in uterine perfusion pressure in pregnant rats

Preeclampsia (PE) is associated with increased total peripheral resistance (TPR), reduced cardiac output (CO), and diminished uterine and placental blood flow. We have developed an animal model that employs chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats to generate a "preeclamptic-like" state during late gestation that is characterized by hypertension, proteinuria, and endothelial dysfunction. Although this animal model has many characteristics of human PE, the systemic hemodynamic and regional changes in blood flow that occur in response to chronic RUPP remains unknown. Therefore, we hypothesized that RUPP would decrease uteroplacental blood flow and CO, and increase TPR. Mean arterial pressure (MAP), CO, cardiac index (CI), TPR, and regional blood flow to various tissues were measured using radiolabeled microspheres in the following two groups of conscious rats: normal pregnant rats (NP; n = 8) and RUPP rats (n = 8). MAP was increased (132 +/- 4 vs. 99 +/- 3 mmHg) in the RUPP rats compared with the NP dams. The hypertension in RUPP rats was associated with increased TPR (2.15 +/- 0.02 vs. 0.98 +/- 0.08 mmHg x ml(-1) x min(-1)) and decreased CI (246 +/- 20 vs. 348 +/- 19 ml x min(-1) x kg(-1), P < 0.002) when contrasted with NP dams. Furthermore, uterine (0.16 +/- 0.03 vs. 0.38 +/- 0.09 ml x min(-1) x g tissue(-1)) and placental blood flow (0.30 +/- 0.08 vs. 0.70 +/- 0.10 ml x min(-1) x g tissue(-1)) were decreased in RUPP compared with the NP dams. These data demonstrate that the RUPP model of pregnancy-induced hypertension has systemic hemodynamic and regional blood flow alterations that are strikingly similar to those observed in women with PE.     

Efficacy of nasal strip and furosemide in mitigating EIPH in Thoroughbred horses.

The purpose of this investigation was to study the effects of an equine nasal strip (NS), furosemide (Fur), and a combination of both (NS + Fur) on exercise-induced pulmonary hemorrhage (EIPH) at speeds corresponding to near-maximal effort. Five Thoroughbreds (526 +/- 25 kg) were run on a flat treadmill from 7 to 14 m/s in 1 m x s(-1) x min(-)1 increments every 2 wk (treatment order randomized) under control (Con), Fur (1 mg/kg iv 4 h prior), NS, or NS + Fur conditions. During each run, pulmonary arterial (Ppa) and esophageal (Pes) pressures were measured. Severity of EIPH was quantified via bronchoalveolar lavage (BAL) 30 min postrun. Furosemide (Fur and NS + Fur trials) reduced peak Ppa approximately 7 mmHg compared with Con (P < 0.05) whereas NS had no effect (P > 0.05). Maximal Pes swings were not different among groups (P > 0.05). NS significantly diminished EIPH compared with the Con trial [Con, 55.0 +/- 36.2; NS, 30.8 +/- 21.8 x 10(6) red blood cells (RBC)/ml BAL fluid; P < 0.05]. Fur reduced EIPH to a greater extent than NS (5.2 +/- 3.0 x 10(6) RBC/ml BAL; P < 0.05 vs. Con and NS) with no additional benefit from NS + Fur (8.5 +/- 4.2 x 10(6) RBC/ml BAL; P > 0.05 vs. Fur, P < 0.05 vs. Con and NS). In conclusion, although both modalities (NS and Fur) were successful in mitigating EIPH, neither abolished EIPH fully as evaluated via BAL. Fur was more effective than NS in constraining the severity of EIPH. The simultaneous use of both interventions appears to offer no further gain with respect to reducing EIPH.     

Venous occlusion to the lower limb attenuates vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia.

We investigated the effects of increases in calf volume on cardiovascular responses during handgrip (HG) exercise and post-HG exercise muscle ischemia (PEMI). Seven subjects completed two trials: one control (no occlusion) and one venous occlusion (VO) session. Both trials included a baseline measurement followed by 15 min of rest (REST), 2 min of HG, and 2 min of PEMI. VO was applied at 100 mmHg via cuffs placed around both distal thighs during REST, HG, and PEMI. Mean arterial pressure, heart rate, forearm blood flow (FBF) in the nonexercised arm, and forearm vascular resistance (FVR) in the nonexercised arm (FVR) were measured. During REST and HG, there were no significant differences between trials in all parameters. During PEMI in the control trial, mean arterial pressure and FVR were significantly greater and FBF was significantly lower than baseline values (P < 0.05 for each). In contrast, in the VO trial, FBF and FVR responses were different from control responses. In the VO trial, FBF was significantly greater than in the control trial (4.7 +/- 0.5 vs. 2.5 +/- 0.3 ml x 100 ml(-1) x min(-1), P < 0.05) and FVR was significantly lower (28.0 +/- 4.8 vs. 49.1 +/- 4.6 units, respectively, P < 0.05). These results indicate that increases in vascular resistance in the nonexercised limb induced by activation of the muscle chemoreflex can be attenuated by increases in calf volume.     

Modulation of arterial baroreflex control of muscle sympathetic nerve activity by muscle metaboreflex in humans

We aimed to investigate the interaction [with respect to the regulation of muscle sympathetic nerve activity (MSNA) and blood pressure] between the arterial baroreflex and muscle metaboreflex in humans. In 10 healthy subjects who performed a 1-min sustained handgrip exercise at 50% maximal voluntary contraction followed by forearm occlusion, arterial baroreflex control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between beat-by-beat spontaneous variations in diastolic arterial blood pressure (DAP) and MSNA both during supine rest (control) and during postexercise muscle ischemia (PEMI). During PEMI (vs. control), 1) the linear relationship between burst incidence and DAP was shifted rightward with no alteration in sensitivity, 2) the linear relationship between burst strength and DAP was shifted rightward and upward with no change in sensitivity, and 3) the linear relationship between total activity and DAP was shifted to a higher blood pressure and its sensitivity was increased. The modification of the control of total activity that occurs in PEMI could be a consequence of alterations in the baroreflex control of both MSNA burst incidence and burst strength. These results suggest that the arterial baroreflex and muscle metaboreflex interact to control both the occurrence and strength of MSNA bursts.     

Oxygen-conserving effects of apnea in exercising men.

We sought to determine whether apnea-induced cardiovascular responses resulted in a biologically significant temporary O(2) conservation during exercise. Nine healthy men performing steady-state leg exercise carried out repeated apnea (A) and rebreathing (R) maneuvers starting with residual volume +3.5 liters of air. Heart rate (HR), mean arterial pressure (MAP), and arterial O(2) saturation (Sa(O(2)); pulse oximetry) were recorded continuously. Responses (DeltaHR, DeltaMAP) were determined as differences between HR and MAP at baseline before the maneuver and the average of values recorded between 25 and 30 s into each maneuver. The rate of O(2) desaturation (DeltaSa(O(2))/Deltat) was determined during the same time interval. During apnea, DeltaSaO(2)/Deltat had a significant negative correlation to the amplitudes of DeltaHR and DeltaMAP (r(2) = 0.88, P < 0.001); i.e., individuals with the most prominent cardiovascular responses had the slowest DeltaSa(O(2))/Deltat. DeltaHR and DeltaMAP were much larger during A (-44 +/- 8 beats/min, +49 +/- 4 mmHg, respectively) than during R maneuver (+3 +/- 3 beats/min, +30 +/- 5 mmHg, respectively). DeltaSa(O(2))/Deltat during A and R maneuvers was -1.1 +/- 0.1 and -2.2 +/- 0.2% units/s, respectively, and nadir Sa(O(2)) values were 58 +/- 4 and 42 +/- 3% units, respectively. We conclude that bradycardia and hypertension during apnea are associated with a significant temporary O(2) conservation and that respiratory arrest, rather than the associated hypoxia, is essential for these responses.     

Exercise training enhances baroreflex control of heart rate by a vagal mechanism in rabbits with heart failure.

Moderate exercise training (Ex) enhances work capacity and quality of life in patients with chronic heart failure (CHF). We investigated the autonomic components of resting heart rate (HR) and the baroreflex control of HR in conscious, instrumented rabbits with pacing-induced CHF after Ex. Sham and CHF rabbits were exercise trained for 4 wk at 15-18 m/min, 6 days/wk. Arterial pressure and HR were recorded before and after metoprolol (1 mg/kg iv) or after atropine (0.2 mg/kg iv). Mean arterial pressure was altered by infusions of sodium nitroprusside and phenylephrine. The data were fit to a sigmoid (logistic) function. Baseline HRs were 266.5 +/- 8.4 and 232.1 +/- 1.6 beats/min in CHF and CHF Ex rabbits, respectively (P < 0.05). In the unblocked state, CHF rabbits had a significantly depressed peak baroreflex slope (1.7 +/- 0.3 vs. 5.6 +/- 0.7 beats. min(-1). mmHg(-1); P < 0.001) and HR range (128.6 +/- 34.5 vs. 253.2 +/- 20.3 beats/min; P < 0.05) compared with normal subjects. Ex increased baroreflex slope to 4.9 +/- 0.3 from 1.7 +/- 0.3 beats. min(-1). mmHg(-1) in unblocked rabbits (P < 0.001 compared with CHF non-Ex). Ex did not alter baroreflex function in sham animals. After metoprolol, baroreflex slope was significantly increased in CHF Ex rabbits (1.5 +/- 0.2 vs. 3.0 +/- 0.2 beats. min(-1). mmHg(-1); P < 0.05). After atropine, there was no significant change in baroreflex slope or HR range between CHF Ex and CHF rabbits. These data support the view that enhancement of baroreflex control of HR after Ex is due to an augmentation of vagal tone.     

Afferent renal denervation impairs baroreflex control of efferent renal sympathetic nerve activity

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which decreases ERSNA to prevent sodium retention. High-sodium diet enhances ARNA, suggesting an important role for ARNA in suppressing ERSNA during excess sodium intake. Mean arterial pressure (MAP) is elevated in afferent renal denervated by dorsal rhizotomy (DRX) rats fed high-sodium diet. We examined whether the increased MAP in DRX is due to impaired arterial baroreflex function. In DRX and sham DRX rats fed high-sodium diet, arterial baroreflex function was determined in conscious rats by intravenous nitroprusside and phenylephrine or calculation of transfer function gain from arterial pressure to ERSNA (spontaneous baroreflex sensitivity). Increasing MAP did not suppress ERSNA to the same extent in DRX as in sham DRX, -60 +/- 4 vs. -77 +/- 6%. Maximum gain, -4.22 +/- 0.45 vs. -6.04 +/- 0.90% DeltaERSNA/mmHg, and the maximum value of instantaneous gain, -4.19 +/- 0.45 vs. -6.04 +/- 0.81% DeltaERSNA/mmHg, were less in DRX than in sham DRX. Likewise, transfer function gain was lower in DRX than in sham DRX, 3.9 +/- 0.2 vs. 6.1 +/- 0.5 NU/mmHg. Air jet stress produced greater increases in ERSNA in DRX than in sham DRX, 35,000 +/- 4,900 vs. 20,900 +/- 3,410%.s (area under the curve). Likewise, the ERSNA responses to thermal cutaneous stimulation were greater in DRX than in sham DRX. These studies suggest impaired arterial baroreflex suppression of ERSNA in DRX fed high-sodium diet. There were no differences in arterial baroreflex function in DRX and sham DRX fed normal-sodium diet. Impaired arterial baroreflex function contributes to increased ERSNA, which would eventually lead to sodium retention and increased MAP in DRX rats fed high-sodium diet.     

心房钠泵因子对颈动脉窦压力感受器反射的易化作用

Effects of atriopeptin II (APII) on the carotid sinus baroreflex in anesthetized rats and on the sinus nerve afferent activity in the anesthetized rabbits were investigated. The results were as follows: (1) By perfusing the isolated left carotid sinus with APII (1 microgram/ml) in anesthetized rats (n = 10), the threshold pressure (TP) of the carotid baroreflex did not show any change, while the equilibrium pressure (EP), the saturation pressure (SP) and the operating range (OR) were decreased from 101 +/- 2.8 to 95 +/- 2.0 mmHg (P less than 0.05), 202 +/- 5.2 to 168 +/- 6.1 mmHg (P less than 0.001) and 128 +/- 5.5 to 93 +/- 6.3 mmHg (P less than 0.001), respectively. The function curve of the baroreflex was shifted to the left and downward with a peak slope (PS) increased during perfusing with APII. In contrast, by perfusing the carotid sinus with sodium nitroprusside (NP, 0.5 micrograms/ml), TP and EP remained unchanged, whereas SP and OR were increased from 188 +/- 6.4 to 218 +/- 6.0 mmHg (n = 6, P less than 0.01) and from 107 +/- 6.9 to 132 +/- 7.6 mmHg (P less than 0.05), respectively. The function curve of the baroreflex and its PS were not affected by NP. The sinus nerve afferent activity was quite stable with the perfusion of carotid sinus at constant intrasinus pressure (ISP) in the rabbits (n = 6) and increased during the elevation of ISP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of morphine on sympathetic nerve activity in humans.

There are conflicting reports for the role of endogenous opioids on sympathetic and cardiovascular responses to exercise in humans. A number of studies have utilized naloxone (an opioid-receptor antagonist) to investigate the effect of opioids during exercise. In the present study, we examined the effect of morphine (an opioid-receptor agonist) on sympathetic and cardiovascular responses at rest and during isometric handgrip (IHG). Eleven subjects performed 2 min of IHG (30% maximum) followed by 2 min of postexercise muscle ischemia (PEMI) before and after systemic infusion of morphine (0.075 mg/kg loading dose + 1 mg/h maintenance) or placebo (saline) in double-blinded experiments on separate days. Morphine increased resting muscle sympathetic nerve activity (MSNA; 17 +/- 2 to 22 +/- 2 bursts/min; P < 0.01) and increased mean arterial pressure (MAP; 87 +/- 2 to 91 +/- 2 mmHg; P < 0.02), but it decreased heart rate (HR; 61 +/- 4 to 59 +/- 3; P < 0.01). However, IHG elicited similar increases for MSNA, MAP, and HR between the control and morphine trial (drug x exercise interaction = not significant). Moreover, responses to PEMI were not different. Placebo had no effect on resting, IHG, and PEMI responses. We conclude that morphine modulates cardiovascular and sympathetic responses at rest but not during isometric exercise.     

Altered muscle metaboreflex control of coronary blood flow and ventricular function in heart failure

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF), coronary vascular conductance (CVC), and regional left ventricular performance in conscious, chronically instrumented dogs during treadmill exercise before and after the induction of heart failure (HF). In control experiments, muscle metaboreflex activation during mild exercise elicited significant reflex increases in mean arterial pressure, heart rate, and cardiac output. CBF increased significantly, whereas no significant change in CVC occurred. There was no significant change in the minimal rate of myocardial shortening (-dl/dt(min)) with muscle metaboreflex activation during mild exercise (15.5 +/- 1.3 to 16.8 +/- 2.4 mm/s, P > 0.05); however, the maximal rate of myocardial relaxation (+dl/dt(max)) increased (from 26.3 +/- 4.0 to 33.7 +/- 5.7 mm/s, P < 0.05). Similar hemodynamic responses were observed with metaboreflex activation during moderate exercise, except there were significant changes in both -dl/dt(min) and dl/dt(max). In contrast, during mild exercise with metaboreflex activation during HF, no significant increase in cardiac output occurred, despite a significant increase in heart rate, inasmuch as a significant decrease in stroke volume occurred as well. The increases in mean arterial pressure and CBF were attenuated, and a significant reduction in CVC was observed (0.74 +/- 0.14 vs. 0.62 +/- 0.12 ml x min(-1) x mmHg(-1); P < 0.05). Similar results were observed during moderate exercise in HF. Muscle metaboreflex activation did not elicit significant changes in either -dl/dt(min) or +dl/dt(max) during mild exercise in HF. We conclude that during HF the elevated muscle metaboreflex-induced increases in sympathetic tone to the heart functionally vasoconstrict the coronary vasculature, which may limit increases in myocardial performance.     

Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.     

Exercise intensity influences cardiac baroreflex function at the onset of isometric exercise in humans.

We sought to examine the influence of exercise intensity on carotid baroreflex (CBR) control of heart rate (HR) and mean arterial pressure (MAP) at the onset of exercise in humans. To accomplish this, eight subjects performed multiple 1-min bouts of isometric handgrip (HG) exercise at 15, 30, 45 and 60% maximal voluntary contraction (MVC), while breathing to a metronome set at eupneic frequency. Neck suction (NS) of -60 Torr was applied for 5 s at end expiration to stimulate the CBR at rest, at the onset of HG (<1 s), and after approximately 40 s of HG. Beat-to-beat measurements of HR and MAP were recorded throughout. Cardiac responses to NS at onset of 15% (-12 +/- 2 beats/min) and 30% (-10 +/- 2 beats/min) MVC HG were similar to rest (-10 +/- 1 beats/min). However, HR responses to NS were reduced at the onset of 45% and 60% MVC HG (-6 +/- 2 and -4 +/- 1 beats/min, respectively; P < 0.001). In contrast to HR, MAP responses to NS were not different from rest at exercise onset. Furthermore, both HR and MAP responses to NS applied at approximately 40s of HG were similar to rest. In summary, CBR control of HR was transiently blunted at the immediate onset of high-intensity HG, whereas MAP responses were preserved demonstrating differential baroreflex control of HR and blood pressure at exercise onset. Collectively, these results suggest that carotid-cardiac baroreflex control is dynamically modulated throughout isometric exercise in humans, whereas carotid baroreflex regulation of blood pressure is well-maintained.     

Effect of sex and ovarian hormones on carotid baroreflex resetting and function during dynamic exercise in humans

To date, no studies have examined whether there are either sex- or ovarian hormone-related alterations in arterial baroreflex resetting and function during dynamic exercise. Thus we studied 16 young men and 18 young women at rest and during leg cycling at 50% heart rate (HR) reserve. In addition, 10 women were studied at three different phases of the menstrual cycle. Five-second pulses of neck pressure (NP) and neck suction (NS) from +40 to -80 Torr were applied to determine full carotid baroreflex (CBR) stimulus response curves. An upward and rightward resetting of the CBR function curve was observed during exercise in all groups with a similar magnitude of CBR resetting for mean arterial pressure (MAP) and HR between sexes (P > 0.05) and at different phases of the menstrual cycle (P > 0.05). For CBR control of MAP, women exhibited augmented pressor responses to NP at rest and exercise during mid-luteal compared with early and late follicular phases. For CBR control of HR, there was a greater bradycardic response to NS in women across all menstrual cycle phases with the operating point (OP) located further away from centering point (CP) on the CBR-HR curve during rest (OP-CP; in mmHg: -13 ± 3 women vs. -3 ± 3 men; P < 0.05) and exercise (in mmHg: -31 ± 2 women vs. -15 ± 3 men; P < 0.05). Collectively, these findings suggest that sex and fluctuations in ovarian hormones do not influence exercise resetting of the baroreflex. However, women exhibited greater CBR control of HR during exercise, specifically against acute hypertension, an effect that was present throughout the menstrual cycle.