Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats

Abstract

Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease (PAD) in which a femoral artery is chronically (~72 hours) ligated, the mechanically-sensitive component of the exercise pressor reflex during 1 Hz dynamic contraction is exaggerated compared to that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats we tested the hypothesis that the increases in mean arterial blood pressure (MAP) and renal sympathetic nerve activity (RSNA) during 1 Hz dynamic stretch are larger when evoked from a previously "ligated" hindlimb compared to those evoked from the contralateral "freely perfused" hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that replicated closely the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in MAP (freely perfused: 14±1, ligated: 23±3 mmHg, p=0.02) and RSNA were significantly greater during dynamic stretch of the ligated hindlimb compared to the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically-sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated PAD involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization.iv

GsMTx4 reduces the reflex pressor response during dynamic hindlimb skeletal muscle stretch in decerebrate rats

“…; Kempf et al. ). An advantage of the model used presently, however, is that mechanoreflex activation produces robust increases in sympathetic nerve activity and blood pressure similar to the increases found during rat hindlimb muscle contraction (Kempf et al.…”

“…We used this protocol recently to investigate mechanoreflex activation during dynamic stretch in decerebrate rats (Kempf et al. ). Approximately 5 min following the completion of the first (i.e., control) dynamic stretch protocol and after ensuring that blood pressure had returned to its prestretch baseline value, we injected lactic acid (0.2 mL of 24 mmol/L concentration in saline) into the arterial supply of the hindlimb via the superficial epigastric artery catheter.…”

“…We recently used such a protocol as an experimental tool to investigate the mechanoreflex signals present during 1 Hz dynamic hindlimb skeletal muscle contraction in decerebrate rats (Kempf et al. ).…”

No effect of endoperoxide 4 or thromboxane A2 receptor blockade on static mechanoreflex activation in rats with heart failure

“…At the end of all experiments in which RSNA was measured, postganglionic sympathetic nerve activity was abolished with administration of hexamethonium bromide (20 mg kg −1 i.v. ) to allow for the quantification of background noise as described previously (Kempf et al., 2018). The decerebrate rats were then killed with an injection of saturated (>3 mg kg −1 ) potassium chloride.…”

The exercise pressor reflex and active O 2 transport in peripheral arterial disease

“…The exaggerated exercise pressor reflex in PAD is primarily attributed to an increased stimulation of mechanosensitive Group III and metabosensitive Group IV muscle afferents (Drew et al, 2013;Stone et al, 2015). This is due, in part, to a greater responsiveness of these fibers to controlled levels of external input, such as capsaicin (Tsuchimochi et al, 2010) and muscle stretch (Kempf et al, 2018). Additionally, oxidative stress and stimulation of acid-sensing ion channels (by changes in pH balance) have been reported to play significant roles in evoking the exaggerated pressor response in both human and animal models of PAD (Tsuchimochi et al, 2011;Muller et al, 2012;Farrag et al, 2017;Harms et al, 2017;Xing et al, 2018).…”