Renal Vasoconstriction in Response to Muscle Mechanoreflex Activation Similar in Young and Older Healthy Humans

Reflex renal vasoconstriction occurs during exercise, and renal vasoconstriction in response to upper-limb muscle mechanoreflex activation has been documented. However, the renal vasoconstrictor response to muscle mechanoreflex activation originating from lower limbs, with and without local metabolite accumulation, has not been assessed. Eleven healthy young subjects (26 ± 1 yr; 5 men) underwent two trials involving 3-min passive calf muscle stretch (mechanoreflex) during 7.5-min lower-limb circulatory occlusion (CO). In one trial, 1.5-min 70% maximal voluntary contraction isometric calf exercise preceded CO to accumulate metabolites during CO and stretch (mechanoreflex and metaboreflex; 70% trial). A control trial involved no exercise before CO (mechanoreflex alone; 0% trial). Beat-to-beat renal blood flow velocity (RBFV; Doppler ultrasound), mean arterial blood pressure (MAP; photoplethysmographic finger cuff), and heart rate (electrocardiogram) were recorded. Renal vascular resistance (RVR), an index of renal vasoconstriction, was calculated as MAP/RBFV. All baseline cardiovascular variables were similar between trials. Stretch increased RVR and decreased RBFV in both trials (change from CO with stretch: RVR – 0% trial = Δ 10 ± 2%, 70% trial = Δ 7 ± 3%; RBFV – 0% trial = Δ −3.8 ± 1.1 cm/s, 70% trial = Δ −2.7 ± 1.5 cm/s; P < 0.05 for RVR and RBFV). These stretch-induced changes were of similar magnitudes in both trials, e.g., with and without local metabolite accumulation, as well as when thromboxane production was inhibited. These findings suggest that muscle mechanoreflex activation via passive calf stretch causes renal vasoconstriction, with and without muscle metaboreflex activation, in healthy humans.

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Hyperadditive ventilatory response arising from interaction between the carotid chemoreflex and the muscle mechanoreflex in healthy humans

Journal of Applied Physiology ◽

10.1152/japplphysiol.00009.2018 ◽

2018 ◽

Vol 125 (1) ◽

pp. 215-225 ◽

Cited By ~ 10

Author(s):

Talita M. Silva ◽

Liliane C. Aranda ◽

Marcelle Paula-Ribeiro ◽

Diogo M. Oliveira ◽

Wladimir M. Medeiros ◽

...

Keyword(s):

Ventilatory Response ◽

Passive Movement ◽

Breathing Frequency ◽

Low Intensity ◽

Healthy Humans ◽

Knee Movement ◽

Neural Interactions ◽

Muscle Mechanoreflex ◽

Low Intensity Exercise ◽

Stimulation Of

Physical exercise potentiates the carotid chemoreflex control of ventilation (VE). Hyperadditive neural interactions may partially mediate the potentiation. However, some neural interactions remain incompletely explored. As the potentiation occurs even during low-intensity exercise, we tested the hypothesis that the carotid chemoreflex and the muscle mechanoreflex could interact in a hyperadditive fashion. Fourteen young healthy subjects inhaled randomly, in separate visits, 12% O2 to stimulate the carotid chemoreflex and 21% O2 as control. A rebreathing circuit maintained isocapnia. During gases administration, subjects either remained at rest (i.e., normoxic and hypoxic rest) or the muscle mechanoreflex was stimulated via passive knee movement (i.e., normoxic and hypoxic movement). Surface muscle electrical activity did not increase during the passive movement, confirming the absence of active contractions. Hypoxic rest and normoxic movement similarly increased VE [change (mean ± SE) = 1.24 ± 0.72 vs. 0.73 ± 0.43 l/min, respectively; P = 0.46], but hypoxic rest only increased tidal volume (Vt), and normoxic movement only increased breathing frequency (BF). Hypoxic movement induced greater VE and mean inspiratory flow (Vt/Ti) increase than the sum of hypoxic rest and normoxic movement isolated responses (VE change: hypoxic movement = 3.72 ± 0.81 l/min vs. sum = 1.96 ± 0.83 l/min, P = 0.01; Vt/Ti change: hypoxic movement = 0.13 ± 0.03 l/s vs. sum = 0.06 ± 0.03 l/s, P = 0.02). Moreover, hypoxic movement increased both Vt and BF. Collectively, the results indicate that the carotid chemoreflex and the muscle mechanoreflex interacted, mediating a hyperadditive ventilatory response in healthy humans. NEW & NOTEWORTHY The main finding of this study was that concomitant carotid chemoreflex and muscle mechanoreflex stimulation provoked greater ventilation increase than the sum of ventilation increase induced by stimulation of each reflex in isolation, which, consequently, supports that the carotid chemoreflex and the muscle mechanoreflex interacted, mediating a hyperadditive ventilatory response in healthy humans.

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Exaggerated muscle mechanoreflex control of reflex renal vasoconstriction in heart failure

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.5.1714 ◽

2001 ◽

Vol 90 (5) ◽

pp. 1714-1719 ◽

Cited By ~ 72

Author(s):

Holly R. Middlekauff ◽

Egbert U. Nitzsche ◽

Carl K. Hoh ◽

Michele A. Hamilton ◽

Gregg C. Fonarow ◽

...

Keyword(s):

Heart Failure ◽

Statistical Significance ◽

Central Command ◽

Renal Vasoconstriction ◽

Involuntary Muscle ◽

Positron Emission ◽

Intact Muscle ◽

Muscle Mechanoreceptor ◽

Muscle Mechanoreflex ◽

Renal Cortical Blood Flow

In heart failure (HF) patients, reflex renal vasoconstriction during exercise is exaggerated. We hypothesized that muscle mechanoreceptor control of renal vasoconstriction is exaggerated in HF. Nineteen HF patients and nineteen controls were enrolled in two exercise protocols: 1) low-level rhythmic handgrip (mechanoreceptors and central command) and 2) involuntary biceps contractions (mechanoreceptors). Renal cortical blood flow was measured by positron emission tomography, and renal cortical vascular resistance (RCVR) was calculated. During rhythmic handgrip, peak RCVR was greater in HF patients compared with controls (37 ± 1 vs. 27 ± 1 units; P < 0.01). Change in (Δ) RCVR tended to be greater as well but did not reach statistical significance (10 ± 1 vs. 7 ± 0.9 units; P = 0.13). RCVR was returned to baseline at 2–3 min postexercise in controls but remained significantly elevated in HF patients. During involuntary muscle contractions, peak RCVR was greater in HF patients compared with controls (36 ± 0.7 vs. 24 ± 0.5 units; P < 0.0001). The Δ RCVR was also significantly greater in HF patients compared with controls (6 ± 1 vs. 4 ± 0.6 units; P = 0.05). The data suggest that reflex renal vasoconstriction is exaggerated in both magnitude and duration during dynamic exercise in HF patients. Given that the exaggerated response was elicited in both the presence and absence of central command, it is clear that intact muscle mechanoreceptor sensitivity contributes to this augmented reflex renal vasoconstriction.

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Renal blood flow in heart failure patients during exercise

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00394.2004 ◽

2004 ◽

Vol 287 (6) ◽

pp. H2834-H2839 ◽

Cited By ~ 32

Author(s):

Afsana Momen ◽

Douglas Bower ◽

John Boehmer ◽

Allen R. Kunselman ◽

Urs A. Leuenberger ◽

...

Keyword(s):

Heart Failure ◽

Blood Flow ◽

Renal Blood Flow ◽

Maximum Voluntary Contraction ◽

Exercise Intolerance ◽

Compensatory Mechanism ◽

Central Command ◽

Renal Vasoconstriction ◽

Muscle Mechanoreflex ◽

Early Phases

During exercise, reflex renal vasoconstriction maintains blood pressure and helps in redistributing blood flow to the contracting muscle. Exercise intolerance in heart failure (HF) is thought to involve diminished perfusion in active muscle. We studied the temporal relationship between static handgrip (HG) and renal blood flow velocity (RBV; duplex ultrasound) in 10 HF and in 9 matched controls during 3 muscle contraction paradigms. Fatiguing HG ( protocol 1) at 40% of maximum voluntary contraction led to a greater reduction in RBV in HF compared with controls (group main effect: P < 0.05). The reduction in RBV early in HG tended to be more prominent during the early phases of protocol 1. Similar RBV was observed in the two groups during post-HG circulatory arrest (isolating muscle metaboreflex). Short bouts (15 s) of HG at graded intensities ( protocol 2; engages muscle mechanoreflex and/or central command) led to greater reductions in RBV in HF than controls ( P < 0.03). Protocol 3, voluntary and involuntary biceps contraction (eliminates central command), led to similar increases in renal vasoconstriction in HF ( n = 4). Greater reductions in RBV were found in HF than in controls during the early phases of exercise. This effect was not likely due to a metaboreflex or central command. Thus our data suggest that muscle mechanoreflex activity is enhanced in HF and serves to vigorously vasoconstrict the kidney. We believe this compensatory mechanism helps preserve blood flow to exercising muscle in HF.

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Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal vasoconstriction during muscle stretch in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00948.2007 ◽

2008 ◽

Vol 294 (5) ◽

pp. H2184-H2190 ◽

Cited By ~ 15

Author(s):

Afsana Momen ◽

Jian Cui ◽

Patrick McQuillan ◽

Lawrence I. Sinoway

Keyword(s):

Animal Studies ◽

Duplex Ultrasound ◽

Muscle Stretch ◽

Renal Vasoconstriction ◽

Block Trial ◽

Before And After ◽

Inhibition Of Prostaglandin Synthesis ◽

Muscle Mechanoreflex ◽

Exercise Muscle ◽

Bier Block

During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal vasoconstriction. Animal studies suggest that prostaglandins generated within the contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that local prostaglandin blockade would attenuate renal vasoconstriction during ischemic muscle stretch. Eleven healthy subjects performed static handgrip before and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG) were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by PHGMI with passive forearm muscle stretch (PHGMI + stretch). Renal vascular resistance (RVR, calculated as MAP/RBV) was increased from baseline during all paradigms except during PHGMI + stretch after the ketorolac Bier block trial where RVR did not change from baseline. Before Bier block, RVR rose more during PHGMI + stretch than during PHGMI alone ( P < .01). Similar results were found after a saline Bier block trial (Δ53 ± 13% vs. Δ35 ± 10%; P < 0.01). However, after ketorolac Bier block, RVR was not greater during PHGMI + stretch than during PHGMI alone [Δ39 ± 8% vs. Δ40 ± 12%; P = not significant (NS)]. HR and MAP responses were similar during PHGMI and PHGMI + stretch ( P = NS). Passive muscle stretch during ischemia augments renal vasoconstriction, suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated constrictor responses. Thus mechanoreceptor sensitization in humans is linked to the production of prostaglandins.

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Splanchnic and renal vasoconstriction during neuropeptide Y infusion in healthy humans

Clinical Physiology ◽

10.1111/j.1475-097x.1992.tb00301.x ◽

1992 ◽

Vol 12 (2) ◽

pp. 145-153 ◽

Cited By ~ 15

Author(s):

G. Ahlborg ◽

E. Weitzberg ◽

J. M. Lundberg

Keyword(s):

Neuropeptide Y ◽

Renal Vasoconstriction ◽

Healthy Humans

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Baroreflex and neurovascular responses to skeletal muscle mechanoreflex activation in humans: an exercise in integrative physiology

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00242.2017 ◽

2017 ◽

Vol 313 (6) ◽

pp. R654-R659 ◽

Cited By ~ 11

Author(s):

Rachel C. Drew

Keyword(s):

Skeletal Muscle ◽

Specific Effect ◽

Future Research ◽

Baroreflex Control ◽

Reflex Mechanism ◽

Integrative Physiology ◽

Renal Vasoconstriction ◽

Exercise Pressor Reflex ◽

Related Disease ◽

Muscle Mechanoreflex

Cardiovascular adjustments to exercise resulting in increased blood pressure (BP) and heart rate (HR) occur in response to activation of several neural mechanisms: the exercise pressor reflex, central command, and the arterial baroreflex. Neural inputs from these feedback and feedforward mechanisms integrate in the cardiovascular control centers in the brain stem and modulate sympathetic and parasympathetic neural outflow, resulting in the increased BP and HR observed during exercise. Another specific consequence of the central neural integration of these inputs during exercise is increased sympathetic neural outflow directed to the kidneys, causing renal vasoconstriction, a key reflex mechanism involved in blood flow redistribution during increased skeletal muscle work. Studies in humans have shown that muscle mechanoreflex activation inhibits cardiac vagal outflow, decreasing the sensitivity of baroreflex control of HR. Metabolite sensitization of muscle mechanoreceptors can lead to reduced sensitivity of baroreflex control of HR, with thromboxane being one of the metabolites involved, via greater inhibition of cardiac vagal outflow without affecting baroreflex control of BP or baroreflex resetting. Muscle mechanoreflex activation appears to play a predominant role in causing renal vasoconstriction, both in isolation and in the presence of local metabolites. Limited investigations in older adults and patients with cardiovascular-related disease have provided some insight into how the influence of muscle mechanoreflex activation on baroreflex function and renal vasoconstriction is altered in these populations. However, future research is warranted to better elucidate the specific effect of muscle mechanoreflex activation on baroreflex and neurovascular responses with aging and cardiovascular-related disease.

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ETA receptors mediate vasoconstriction, whereas ETB receptors clear endothelin-1 in the splanchnic and renal circulation of healthy men

Clinical Science ◽

10.1042/cs1040143 ◽

2003 ◽

Vol 104 (2) ◽

pp. 143-151 ◽

Cited By ~ 24

Author(s):

Felix BÖHM ◽

John PERNOW ◽

Jonas LINDSTRÖM ◽

Gunvor AHLBORG

Keyword(s):

Receptor Antagonist ◽

Vascular Resistance ◽

Vascular Tone ◽

Renal Vasoconstriction ◽

Healthy Humans ◽

Arterial Blood ◽

Eta Receptor ◽

Etb Receptor ◽

Eta Receptor Antagonist ◽

Renal Vascular

The contribution of the endothelin (ET) receptors ETA and ETB to basal vascular tone and ET-1-induced vasoconstriction in the renal and splanchnic vasculature was investigated in six healthy humans. ET-1 was infused alone and in combination with the selective ETA receptor antagonist BQ123 or the selective ETB receptor antagonist BQ788 on three different occasions. BQ123 did not affect basal arterial blood pressure, splanchnic vascular resistance (SplVR) or renal vascular resistance (RVR), but inhibited the increase in vascular resistance induced by ET-1 [64±18 versus -1±7% in SplVR (P<0.05); 36±6 versus 12±3% in RVR (P<0.0001)]. BQ788 increased basal SplVR and RVR [38±16% (P = 0.01) and 21±5% (P<0.0001) respectively], and potentiated the ET-1-induced vasoconstriction. Plasma ET-1 increased more after ETB blockade than under control conditions or after ETA blockade. These findings suggest that the ETA receptor mediates the splanchnic and renal vasoconstriction induced by ET-1 in healthy humans. The ETB receptor seems to function as a clearance receptor and may modulate vascular tone by altering the plasma concentration of ET-1.

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A perspective on the muscle reflex: implications for congestive heart failure

Journal of Applied Physiology ◽

10.1152/japplphysiol.01405.2004 ◽

2005 ◽

Vol 99 (1) ◽

pp. 5-22 ◽

Cited By ~ 85

Author(s):

Lawrence I. Sinoway ◽

Jianhua Li

Keyword(s):

Heart Failure ◽

Muscle Afferents ◽

Receptor Subtype ◽

Renal Vasoconstriction ◽

Exercise Pressor Reflex ◽

Acid Sensing Ion Channels ◽

Health And Disease ◽

Reflex Activation ◽

Muscle Mechanoreflex ◽

Muscle Reflex

In this review we examine the exercise pressor reflex in health and disease. The role of metabolic and mechanical stimulation of thin fiber muscle afferents is discussed. The role ATP and lactic acid play in stimulating and sensitizing these afferents is examined. The role played by purinergic receptors subdivision 2, subtype X, vanilloid receptor subtype 1, and acid-sensing ion channels in mediating the effects of ATP and H+ are discussed. Muscle reflex activation in heart failure is then examined. Data supporting the concept that the metaboreflex is attenuated and that the mechanoreflex is accentuated are presented. The role the muscle mechanoreflex plays in evoking renal vasoconstriction is also described.

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