Isolated activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) using post-exercise ischaemia (PEI) following handgrip partially maintains exercise-induced increases in arterial blood pressure (BP) and muscle sympathetic nerve activity (SNA), while heart rate (HR) declines towards resting values. Although masking of metaboreflex-mediated increases in cardiac SNA by parasympathetic reactivation during PEI has been suggested, this has not been directly tested in humans. In nine male subjects (23 ± 5 years) the muscle metaboreflex was activated by PEI following moderate (PEI-M) and high (PEI-H) intensity isometric handgrip performed at 25% and 40% maximum voluntary contraction, under control (no drug), parasympathetic blockade (glycopyrrolate) and β-adrenergic blockade (metoprolol or propranalol) conditions, while beat-to-beat HR and BP were continuously measured. During control PEI-M, HR was slightly elevated from rest (+3 ± 2 beats min −1 ); however, this HR elevation was abolished with β-adrenergic blockade (P < 0.05 vs. control) but augmented with parasympathetic blockade (+8 ± 2 beats min −1 , P < 0.05 vs. control and β-adrenergic blockade). The HR elevation during control PEI-H (+9 ± 3 beats min −1 ) was greater than with PEI-M (P < 0.05), and was also attenuated with β-adrenergic blockade (+4 ± 2 beats min −1 , P < 0.05 vs. control), but was unchanged with parasympathetic blockade (+9 ± 2 beats min −1 , P > 0.05 vs. control). BP was similarly increased from rest during PEI-M and further elevated during PEI-H (P < 0.05) in all conditions. Collectively, these findings suggest that the muscle metaboreflex increases cardiac SNA during PEI in humans; however, it requires a robust muscle metaboreflex activation to offset the influence of cardiac parasympathetic reactivation on heart rate.

Key points• The influence of normative ageing on cerebral perfusion, oxygenation and metabolism during exercise is not well known.• This study assessed cerebral perfusion and concentration differences for oxygen, glucose and lactate across the brain, in young and elderly individuals at rest and during incremental exercise to exhaustion.• We observed that during submaximal exercise (at matched relative intensities) and during maximal exercise, cerebral perfusion was reduced in older individuals compared with young individuals, while the cerebral metabolic rate for oxygen and uptake of glucose and lactate were similar.• The results indicate that the age-related reduction in cerebral perfusion during exercise does not affect brain uptake of lactate and glucose.Abstract We evaluated cerebral perfusion, oxygenation and metabolism in 11 young (22 ± 1 years) and nine older (66 ± 2 years) individuals at rest and during cycling exercise at low (25% W max ), moderate (50% W max ), high (75% W max ) and exhaustive (100% W max ) workloads. Mean middle cerebral artery blood velocity (MCA V mean ), mean arterial pressure (MAP), cardiac output (CO) and partial pressure of arterial carbon dioxide (P aCO 2 ) were measured. Blood samples were obtained from the right internal jugular vein and brachial artery to determine concentration differences for oxygen (O 2 ), glucose and lactate across the brain. The molar ratio between cerebral uptake of O 2 versus carbohydrate (O 2 -carbohydrate index; O 2 /[glucose + 1/2 lactate]; OCI), the cerebral metabolic rate of O 2 (CMRO 2 ) and changes in mitochondrial O 2 tension (P mitoO 2 ) were calculated. 100% W max was ∼33% lower in the older group. Exercise increased MAP and CO in both groups (P < 0.05 vs. rest), but at each intensity MAP was higher and CO lower in the older group (P < 0.05). MCA V mean , P aCO 2 and cerebral vascular conductance index (MCA V mean /MAP) were lower in the older group at each exercise intensity (P < 0.05). In contrast, young and older individuals exhibited similar increases in CMRO 2 (by ∼30 μmol (100 g −1 ) min −1 ), and decreases in OCI (by ∼1.5) and P mitoO 2 (by ∼10 mmHg) during exercise at ≥75% W max . Thus, despite the older group having reduced cerebral perfusion and maximal exercise capacity, cerebral oxygenation and uptake of lactate and glucose are similar during exercise in young and older individuals. Abbreviations CBF, cerebral blood flow; CMRO 2 , cerebral metabolic rate for oxygen; CO, cardiac output; HR, heart rate; MAP, mean arterial pressure; MCA V mean , middle cerebral artery mean blood velocity; OCI, oxygen-to-carbohydrate index; OGI, oxygen-to-glucose index; P aCO 2 , partial pressure of arterial carbon dioxide; P capO 2 , cerebral capillary oxygen tension; P mitoO 2 , mitochondrial oxygen tension; S capO 2 , cerebral capillary oxygen saturation; SV, stroke volume; VC, vascular conductance; W max , maximal power achieved during the incremental exercise protocol.

Kim A, Deo SH, Vianna LC, Balanos GM, Hartwich D, Fisher JP, Fadel PJ. Sex differences in carotid baroreflex control of arterial blood pressure in humans: relative contribution of cardiac output and total vascular conductance. Am J Physiol Heart Circ Physiol 301: H2454 -H2465, 2011. First published September 30, 2011 doi:10.1152/ajpheart.00772.2011.-It is presently unknown whether there are sex differences in the magnitude of blood pressure (BP) responses to baroreceptor perturbation or if the relative contribution of cardiac output (CO) and total vascular conductance (TVC) to baroreflex-mediated changes in BP differs in young women and men. Since sympathetic vasoconstrictor tone is attenuated in women, we hypothesized that carotid baroreflex-mediated BP responses would be attenuated in women by virtue of a blunted vascular response (i.e., an attenuated TVC response). BP, heart rate (HR), and stroke volume were continuously recorded during the application of 5-s pulses of neck pressure (NP; carotid hypotension) and neck suction (NS; carotid hypertension) ranging from ϩ40 to Ϫ80 Torr in women (n ϭ 20, 21 Ϯ 0.5 yr) and men (n ϭ 20, 21 Ϯ 0.4 yr). CO and TVC were calculated on a beat-to-beat basis. Women demonstrated greater depressor responses to NS (e.g., Ϫ60 Torr, Ϫ17 Ϯ 1%baseline in women vs. Ϫ11 Ϯ 1%baseline in men, P Ͻ 0.05), which were driven by augmented decreases in HR that, in turn, contributed to larger reductions in CO (Ϫ60 Torr, Ϫ15 Ϯ 2%baseline in women vs. Ϫ6 Ϯ 2%baseline in men, P Ͻ 0.05). In contrast, pressor responses to NP were similar in women and men (e.g., ϩ40 Torr, ϩ14 Ϯ 2%baseline in women vs. ϩ10 Ϯ 1%baseline in men, P Ͼ 0.05), with TVC being the primary mediating factor in both groups. Our findings indicate that sex differences in the baroreflex control of BP are evident during carotid hypertension but not carotid hypotension. Furthermore, in contrast to our hypothesis, young women exhibited greater BP responses to carotid hypertension by virtue of a greater cardiac responsiveness. arterial baroreceptors; gender; heart rate; stroke volume; total peripheral resistance THE ARTERIAL BAROREFLEX plays an important role in the beatto-beat regulation of arterial blood pressure (BP). These rapid baroreflex adjustments are mediated by alterations in autonomic neural activity to the heart and vasculature, which modulates cardiac output (CO) and total vascular conductance (TVC), respectively (19,48). Studies (7, 10) in animals have demonstrated that baroreflex-mediated heart rate (HR) responses are greater in female rodents compared with male rodents. However, limited studies have been performed in humans, and equivocal results have been reported. Indeed, compared with young men, young women have been reported to exhibit similar, increased, or decreased cardiac baroreflex control (1, 8, 13, 59). In addition, the majority of these studies used pharmacological approaches to examine arterial baroreflex function, which do not permit an assessment of BP responses to baroreflex perturbation. Thus, to date,...

Non-technical summary The 'arterial baroreflex' plays an important role in the momentto-moment regulation of blood pressure. It does this partly by eliciting changes in heart rate, but its ability to do this (i.e. sensitivity) during exercise is reduced from rest. During exercise, chemicals accumulate in the muscles (i.e. metabolites) that stimulate sensory nerves within the muscle (i.e. muscle metaboreflex). We show for the first time in humans that the stimulation of metabolically sensitive nerves within the muscles during leg cycling exercise decreases arterial baroreflex sensitivity. This new knowledge increases our understanding of the control of the human heart during exercise.Abstract We sought to determine whether the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans. In protocol 1, 15 male subjects (22 ± 1 years) performed steady-state leg cycling at low (26 ± 4 W) and moderate workloads (105 ± 7 W), under free-flow conditions and with partial flow restriction (bilateral thigh cuff inflation at 100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2, rhythmic handgrip exercise at 35% maximum voluntary contraction was performed with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs. rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 ± 2, 7 ± 1 and 2 ± 0.2 ms mmHg −1 at rest, low and moderate workloads, respectively; P < 0.05), which was further reduced with partial flow restriction (by -2.6 ± 0.8 and -0.4 ± 0.1 ms mmHg −1 at low and moderate workloads). cBRS remained suppressed during PEI following leg cycling with partial flow restriction (4 ± 1 ms mmHg −1 ; P < 0.05 vs. rest). cBRS was unchanged during handgrip under free-flow conditions, handgrip with partial flow restriction and PEI following handgrip (P > 0.05 vs. rest). These data indicate that the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases cardiac baroreflex responsiveness during leg cycling exercise in humans. Abbreviations BP, blood pressure; cBRS, cardiac baroreflex sensitivity; ECG, electrocardiogram; Ex90/120, leg cycling at target heart rate of 90/120 beats min −1 ; Ex +80/+100/+120, rhythmic handgrip exercise with arm cuff at 80/100/120 mmHg; FBF, forearm blood flow; FBV, forearm blood velocity; HR, heart rate; HR-cBRS, spontaneous cardiac baroreflex sensitivity calculated using heart rate; FF, free flow; MVC, maximum voluntary contraction; PEI, post-exercise ischaemia; PFR, partial flow restriction; RMSSD, square root of the mean of successive differences in ...

Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exerciseinduced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral metabolism (from arterial and internal jugular venous O 2 , glucose and lactate differences), as well as the middle cerebral artery mean blood velocity (MCA V mean ; transcranial Doppler ultrasound) during a sustained static handgrip contraction at 40% of maximal voluntary contraction (n = 9) and the MCA V mean during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from ∼60 to ∼110 beats min −1 (P < 0.01) and cardiac output by ∼40% (P < 0.05), but did not affect mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate. Glycopyrrolate did not significantly affect cerebral metabolism during static handgrip, but a parallel increase in MCA V mean (∼16%; P < 0.01) and CBF (∼12%; P < 0.01) during static handgrip, as well as the increase in MCA V mean during cycling (∼15%; P < 0.01), were abolished by glycopyrrolate (P < 0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen.