Reflex cardiovascular and ventilatory responses to increasing H+ activity in cat hindlimb muscle

117

174

Metabolic products of skeletal muscle contraction activate metaboreceptor muscle afferents that reflexively increase sympathetic nerve activity (SNA) targeted to both resting and exercising skeletal muscle. To determine effects of the increased sympathetic vasoconstrictor drive on muscle oxygenation, we measured changes in tissue oxygen stores and mitochondrial cytochrome a,a 3 redox state in rhythmically contracting human forearm muscles with near infrared spectroscopy while simultaneously measuring muscle SNA with microelectrodes. The major new finding is that the ability of reflex-sympathetic activation to decrease muscle oxygenation is abolished when the muscle is exercised at an intensity Ͼ 10% of maximal voluntary contraction (MVC). During high intensity handgrip (45% MVC), contractioninduced decreases in muscle oxygenation remained stable despite progressive metaboreceptor-mediated reflex increases in SNA. During mild to moderate handgrips (20-33% MVC) that do not evoke reflex-sympathetic activation, experimentally induced increases in muscle SNA had no effect on oxygenation in exercising muscles but produced robust decreases in oxygenation in resting muscles. The latter decreases were evident even during maximal metabolic vasodilation accompanying reactive hyperemia.We conclude that in humans sympathetic neural control of skeletal muscle oxygenation is sensitive to modulation by metabolic events in the contracting muscles. These events are different from those involved in either metaboreceptor muscle afferent activation or reactive hyperemia. ( J. Clin. Invest. 1996. 98:584-596.)

Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Differential sympathetic neural control of oxygenation in resting and exercising human skeletal muscle.

Hansen¹,

Thomas²,

Harris³

et al. 1996

117

174

“…It has been proposed that hydrogen ions are involved in muscle afferent activation. In favor of this proposal, it was found that a decrease in muscle intracellular pH parallels the increase in muscle sympathetic activity in response to isometric exercise (13,14). Furthermore, muscle contraction in patients with muscle phosphorylase deficiency (McArdle's disease) is not accompanied by glycogen degradation or a decrease in muscle pH, and MSNA does not increase in response to isometric exercise in these patients (15).…”

Section: Discussionmentioning

confidence: 99%

Role of adenosine in the sympathetic activation produced by isometric exercise in humans.

Costa¹,

Biaggioni²

1994

Isometric exercise increases sympathetic nerve activity and blood pressure. This exercise pressor reflex is partly mediated by metabolic products activating muscle afferents (metaboreceptors). Whereas adenosine is a known inhibitory neuromodulator, there is increasing evidence that it activates afferent nerves. We, therefore, examined the hypothesis that adenosine stimulates muscle afferents and participates in the exercise pressor reflex in healthy volunteers. Intraarterial administration of adenosine into the forearm, during venous occlusion to prevent systemic effects, mimicked the response to exercise, increasing muscle sympathetic nerve activity (MSNA, lower limb microneurography) and mean arterial blood pressure (MABP) at all doses studied (2, 3, and 4 mg). Heart rate increased only with the highest dose. Intrabrachial adenosine (4 mg) increased MSNA by 96±25% (n = 6, P < 0.01) and MABP by 12±3 mmHg (P < 0.01). Adenosine produced forearm discomfort, but equivalent painful stimuli (forearm ischemia and cold exposure) increased MSNA significantly less than adenosine. Furthermore, adenosine receptor antagonism with intrabrachial theophylline (1 ytg/ml forearm per min) blocked the increase in MSNA (92±15% vs. 28±6%, n = 7, P < 0.01) and MABP (38±6 vs. 27±4 mmHg, P = 0.01) produced by isometric handgrip (30% of maximal voluntary contraction) in the infused arm, but not the contralateral arm. Theophylline did not prevent the increase in heart rate produced by handgrip, a response mediated more by central command than muscle afferent activation. We propose that endogenous adenosine contributes to the activation of muscle afferents involved in the exercise pressor reflex in humans. (J. Clin. Invest.

“…Specifically, pH responses were attenuated in the bodybuilders (F = 4.7; P < 0.05, Fig. 2 A) with significant differences between the two subject groups during the 2 min of static exercise (bodybuilders, 6.99; normal volunteers, 6.89; P < 0.02) and during the 2 min of PHG-CA (minute 1 of PHG-CA: bodybuilders, 6.88; normal volunteers, 6.79; P < 0.02; minute 2 of PHG-CA: bodybuilders, 6.86; normal volunteers, 6.78; P < 0.04). We observed no effect of dominance on the pH response to static exercise during this protocol (Fig.…”

Section: Experimental Protocolsmentioning

confidence: 95%

“…Based on these classic studies it has been suggested that during exercise, muscle ischemia contributes to an increase in sympathetic outflow through activation ofa muscle metaboreflex. The skeletal muscle metabolic events that initiate and sustain this reflex response are not entirely clear, although experiments from a number oflaboratories suggest an important role for skeletal muscle lactic acid production and/or reductions in muscle pH (2)(3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans.

Sinoway¹,

Rea²,

Mosher³

et al. 1992

We examined the effects of exercise conditioning on muscle sympathetic nerve activity (MSNA) during handgrip and posthandgrip circulatory arrest (PHG-CA). Two conditioning stimuli were studied: forearm dominance and bodybuilding. Static handgrip at 30% maximal voluntary contraction followed by PHG-CA led to a rise in MSNA smaller in dominant than in nondominant forearms (99% vs. 222%; P < 0.02) and in body builders than in normal volunteers (28% vs. 244%; P < 0.01). Separate 31P NMR experiments showed no effect of dominance on forearm pH but a pH in bodybuilders higher (6.88) than in normal volunteers (6.79; P < 0.02) during PHG-CA.Our second goal was to determine if factors besides attenuated [H'J contribute to this conditioning effect. If differences in MSNA during exercise were noted at the same pH, then other mechanisms must contribute to the training effect. We measured MSNA during ischemic fatiguing handgrip. No dominance or bodybuilding effect on pH was noted. However, we noted increases in MSNA smaller in dominant than nondominant forearms (212% vs. 322%; P < 0.02) and in bodybuilders than in normal volunteers (161% vs. 334%; P < 0.01). In summary, MSNA responses were less during exercise of conditioned limbs. Factors aside from a lessening of muscle acidosis contribute to this effect. (J. Clin. Invest. 1992.