We tested the hypotheses that arterial baroreflex (ABR) control over muscle sympathetic nerve activity (MSNA) in humans does not remain constant throughout a bout of leg cycling ranging in intensity from very mild to exhausting. ABR control over MSNA (burst incidence, burst strength and total MSNA) was evaluated by analysing the relationship between beat-to-beat spontaneous variations in diastolic arterial pressure (DAP) and MSNA in 15 healthy subjects at rest and during leg cycling in a seated position at five workloads: very mild (10 W), mild (82 ± 5.0 W), moderate (126 ± 10.2 W), heavy (156 ± 14.3 W), and exhausting (190 ± 21.2 W). The workload was incremented every 6 min. The linear relationships between DAP and MSNA variables were significantly shifted downward during very mild exercise, but then shifted progressively upward as exercise intensity increased. During heavy and exhausting exercise, moreover, the DAP-MSNA relationships were also significantly shifted rightward from the resting relationship. The sensitivity of ABR control over burst incidence and total MSNA was significantly lower during very mild exercise than during rest, and the sensitivity of the burst incidence control remained lower than the resting level at all higher exercise intensities. By contrast, the sensitivity of the total MSNA control recovered to the resting level during mild and moderate exercise, and was significantly increased during heavy and exhausting exercise (versus rest). We conclude that, in humans, ABR control over MSNA is not uniform throughout a leg cycling exercise protocol in which intensity was varied from very mild to exhausting. We suggest that this non-uniformity of ABR function is one of the mechanisms by which sympathetic and cardiovascular responses are matched to the exercise intensity.

We investigated the time-dependent modulation of arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) that occurs during isometric handgrip exercise (IHG). Thirteen healthy subjects performed a 3-min IHG at 30% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). The ABR control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between spontaneous variations in diastolic arterial pressure (DAP) and MSNA during supine rest, at each minute of IHG, and during PEMI. We found that 1) the linear relations between DAP and MSNA variables were shifted progressively rightward until the third minute of IHG (IHG3); 2) 2 min into IHG (IHG2), the DAP-MSNA relations were shifted upward and were shifted further upward at IHG3; 3) the sensitivity of the ABR control of total MSNA was increased at IHG2 and increased further at IHG3; and 4) during PEMI, the ABR operating pressure was slightly higher than at IHG2, and the sensitivity of the control of total MSNA was the same as at IHG2. During PEMI, the DAP-burst strength and DAP-total MSNA relations were shifted downward from the IHG3 level to the IHG2 level, whereas the DAP-burst incidence relation remained at the IHG3 level. These results indicate that during IHG, ABR control of MSNA is modulated in a time-dependent manner. We suggest that this modulation of ABR function is one of the mechanisms underlying the progressive increase in blood pressure and MSNA during the course of isometric exercise.

We aimed to investigate the interaction between the arterial baroreflex and muscle metaboreflexes (as reflected by alterations in the dynamic responses shown by muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP) and heart rate (HR)) in humans. In nine healthy subjects (eight male, one female) who performed a sustained 1 min handgrip exercise at 50 % maximal voluntary contraction followed by forearm occlusion, a 5 s period of neck pressure (NP) (30 and 50 mmHg) or neck suction (NS)(_30 and _60 mmHg) was used to evaluate carotid baroreflex function at rest (CON) and during post-exercise muscle ischaemia (PEMI). In PEMI (as compared with CON): (a) the augmentations in MSNA and MAP elicited by 50 mmHg NP were both greater; (b) MSNA seemed to be suppressed by NS for a shorter period, (c) the decrease in MAP elicited by NS was smaller, and (d) MAP recovered to its initial level more quickly after NS. However, the HR responses to NS and NP were not different between PEMI and CON. These results suggest that during muscle metaboreflex activation, the dynamic arterial baroreflex response is modulated, as exemplified by the augmentation of the MSNA response to arterial baroreflex unloading (i.e. NP) and the reduction in the suppression of MSNA induced by baroreceptor stimulation (i.e. NS).

Muscle metaboreflex activation (MMA) during dynamic exercise increases cardiac work and myocardial O2 demand via increases in heart rate, ventricular contractility, and afterload. This increase in cardiac work should lead to metabolic coronary vasodilation; however, no change in coronary vascular conductance occurs. This indicates that the MMA-induced increase in sympathetic activity to the heart, which raises heart rate, ventricular contractility, and cardiac output, also elicits coronary vasoconstriction. In heart failure, cardiac output does not increase with MMA presumably due to impaired ability to improve left ventricular contractility. In this setting actual coronary vasoconstriction is observed. We tested whether this coronary vasoconstriction could explain, in part, the reduced ability to increase cardiac performance during MMA. In conscious, chronically instrumented dogs before and after pacing-induced heart failure, MMA responses during mild exercise were observed before and after α1-adrenergic blockade (prazosin 20-50 μg/kg). During MMA, the increases in coronary vascular conductance, coronary blood flow, maximal rate of left ventricular pressure change, and cardiac output were significantly greater after α1-adrenergic blockade. We conclude that in subjects with heart failure, coronary vasoconstriction during MMA limits the ability to increase left ventricular contractility.

Ichinose, Masashi, Mitsuru Saito, Hiroyuki Wada, Asami Kitano, Narihiko Kondo, and Takeshi Nishiyasu. Modulation of arterial baroreflex control of muscle sympathetic nerve activity by muscle metaboreflex in humans. Am J Physiol Heart Circ Physiol 286: H701-H707, 2004; 10.1152/ajpheart.00618.2003.-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 beatby-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. skeletal muscle metaboreflex; arterial blood pressure; exercise STATIC AND DYNAMIC EXERCISE is accompanied by increases in arterial blood pressure, heart rate (HR), and sympathetic nerve activity (SNA). These cardiovascular responses are hypothesized to be mediated by a number of factors: 1) central command (24), 2) feedback mechanisms via the afferent nerves (group III and IV fibers) arising from the working skeletal muscles (16,17,23), and 3) arterial and cardiopulmonary baroreflexes (23,24). It has been hypothesized that during heavy exercise the arterial baroreflexes and muscle metaboreflexes are both activated and that they interact to regulate the responses shown by blood pressure, HR, and SNA levels (8-10, 18, 21, 22, 29, 31).Two types of interaction between arterial baroreflexes and muscle metaboreflexes in the control of cardiovascular responses have been demonstrated. The first involves arterial baroreflexes opposing the pressor response elicited via the muscle metaboreflexes (18,21,29,31). Evidence for this opposing effect of the arterial baroreflexes has been obtained during dynamic exercise in dogs (31) as well as during static handgrip exercise (29) and postexercise muscle ischemia (PEMI) in humans (18). The second type of interaction is a modulation of arterial baroreflex function during muscle metaboreflex activation (8-10, 22). Indeed, Papelier et al....

Gender-specific differences exist in the incidence and age distribution of the various types of idiopathic VT. Studies on gender-specific differences in arrhythmia will lead to a better understanding of its mechanism(s) and provide valuable information for the development of optimal treatment strategies.

Muscle metaboreflex activation during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility, and afterload. This increase in cardiac work should cause coronary metabolic vasodilation. However, little if any coronary vasodilation is observed due to concomitant sympathetically induced coronary vasoconstriction. The purpose of the present study is to determine whether the restraint of coronary vasodilation functionally limits increases in left ventricular contractility. Using chronically instrumented, conscious dogs (n = 9), we measured mean arterial pressure, cardiac output, and circumflex blood flow and calculated coronary vascular conductance, maximal derivative of ventricular pressure (dp/dt(max)), and preload recruitable stroke work (PRSW) at rest and during mild exercise (2 mph) before and during activation of the muscle metaboreflex. Experiments were repeated after systemic alpha(1)-adrenergic blockade ( approximately 50 microg/kg prazosin). During prazosin administration, we observed significantly greater increases in coronary vascular conductance (0.64 + or - 0.06 vs. 0.46 + or - 0.03 ml x min(-1) x mmHg(-1); P < 0.05), circumflex blood flow (77.9 + or - 6.6 vs. 63.0 + or - 4.5 ml/min; P < 0.05), cardiac output (7.38 + or - 0.52 vs. 6.02 + or - 0.42 l/min; P < 0.05), dP/dt(max) (5,449 + or - 339 vs. 3,888 + or - 243 mmHg/s; P < 0.05), and PRSW (160.1 + or - 10.3 vs. 183.8 + or - 9.2 erg.10(3)/ml; P < 0.05) with metaboreflex activation vs. those seen in control experiments. We conclude that the sympathetic restraint of coronary vasodilation functionally limits further reflex increases in left ventricular contractility.

-To investigate local bloodflow regulation during orthostatic maneuvers, 10 healthy subjects were exposed to Ϫ20 and Ϫ40 mmHg lower body negative pressure (LBNP; each for 3 min) and to 60°head-up tilt (HUT; for 5 min). Measurements were made of blood flow in the brachial (BFbrachial) and femoral arteries (BF femoral) (both by the ultrasound Doppler method), heart rate (HR), mean arterial pressure (MAP), cardiac stroke volume (SV; by echocardiography), and left ventricular enddiastolic volume (LVEDV; by echocardiography). Comparable central cardiovascular responses (changes in LVEDV, SV, and MAP) were seen during LBNP and HUT. During Ϫ20 mmHg LBNP, Ϫ40 mmHg LBNP, and HUT, the following results were observed: 1) BFbrachial decreased by 51, 57, and 41%, and BFfemoral decreased by 40, 53, and 62%, respectively, 2) vascular resistance increased in the upper limb by 110, 147, and 85%, and in the lower limb by 76, 153, and 250%, respectively. The increases in vascular resistance were not different between the upper and lower limbs during LBNP. However, during HUT, the increase in the lower limb was much greater than that in the upper limb. These results suggest that, during orthostatic stimulation, the vascular responses in the limbs due to the cardiopulmonary and arterial baroreflexes can be strongly modulated by local mechanisms (presumably induced by gravitational effects). blood flow; orthostatic stress; baroreflex IT IS KNOWN THAT, DURING ORTHOSTATIC stress, peripheral vascular resistance and/or heart rate (HR) increase (mainly via cardiopulmonary and arterial baroreflexes), serving to maintain arterial blood pressure (1, 3-5, 7, 8, 17, 27, 36, 37, 39, 42, 44, 47). Furthermore, it has been suggested that, during orthostatic stress, differential vascular responses occur between the arms and legs (9, 12, 16). The proposed explanations for the latter phenomenon include differences in 1) "local" mechanisms stimulated by the increments in transmural pressure (11,12,18), 2) norepinephrine spillover (13), and 3) the effectiveness of ␣-or ␤-receptors (26). However, those mechanisms are not well understood.Various ways can be used to simulate orthostatic stress in humans. These include application of lower body negative pressure (LBNP) and head-up tilt (HUT), which are known to increase the pooling of blood in the lower body, leading to a decreased blood volume in the central circulation and a consequent unloading of cardiopulmonary and arterial baroreceptors. LBNP is usually applied with the subject in the horizontal posture, and the negative pressure affects mainly the superficial veins, less so the arteries, so arterial blood pressure is almost constant throughout the whole body. In contrast, during HUT, the arterial and venous pressures increase in proportion to the distance from the heart. Thus LBNP and HUT represent two possible ways of decreasing the central blood volume and enhancing sympathetic nervous activity, but they differ in the extent of the change in hydrostatic pressure (local pressure) in the dependent ...