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

Abstract

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.

Keywords: baroreflex; exercise; mechanoreflex; metabolite sensitization; renal vasoconstriction.

Fig. 1.

Schematic representation of the neural interactions involving skeletal muscle mechanoreflex activation, with additional muscle metaboreflex activation, and the arterial baroreflex, as well as resultant neurovascular alterations affecting the kidneys, heart, and systemic vasculature. Orange arrow, metabolite sensitization of muscle mechanoreceptors. Green arrows, afferent neural input. Purple arrow, central command neural input. Blue arrow, vagal efferent output. Red arrows, sympathetic efferent output.

Fig. 2.

Maximal gain (sensitivity) of carotid-cardiac (control of heart rate; A) and carotid-vasomotor (control of blood pressure; B) baroreflex function curves during passive right calf muscle stretch with concurrent lower-limb circulatory occlusion in the following trials: prior ischemic noncalf-exercise control in the left limb (ICL), prior ischemic isometric calf exercise at 50% maximal voluntary contraction for 1.5 min in the left limb (IEL), prior ischemic noncalf-exercise control in the right limb (ICR), and prior ischemic isometric calf exercise at 50% maximal voluntary contraction for 1.5 min in the right limb (IER) (n = 12 for A and B). Dark shading represents concurrent muscle mechanoreflex activation and muscle metaboreflex activation in the same limb. Light shading represents concurrent muscle mechanoreflex activation with muscle metaboreflex activation in the contralateral limb. *Significantly different from IEL, P < 0.05. From Drew et al. (15) with permission.

Fig. 3.

A: relative change from baseline in renal vascular resistance (RVR) during end-rest/exercise, circulatory occlusion (CO), and CO with passive right calf muscle stretch (CO+stretch) in the following trials: prior noncalf-exercise control in the right limb (0%) and prior isometric calf exercise at 70% maximal voluntary contraction for 1.5 min in the right limb (70%; n = 11). B: relative change from CO in RVR during CO+stretch in the following trials: prior noncalf-exercise control in the right limb (0%) and prior isometric calf exercise at 70% maximal voluntary contraction for 1.5 min in the right limb (70%; n = 11). *Significantly different from 0% (P < 0.05). †Significantly different between phases (P < 0.05). ‡Significantly different from 0% at specific time point (P < 0.05). From Drew et al. (13).

Fig. 4.

Change in (Δ) increase in renal cortical vascular resistance (RCVR) during involuntary electrically evoked biceps muscle contractions for 10 s within every 15 s for 3 min in heart failure patients (n = 9) and healthy, age-matched control participants (Normal; n = 10). From Middlekauff et al. (39).