Lactate and hydrogen ions play a predominant role in evoking the exercise pressor reflex during ischemic contractions but not during freely perfused contractions
Authors: Ducrocq Guillaume , Herold Paul , Higgins Shannon , Anselmi Laura , Ruiz-Velasco Victor , Kaufman Marc 
Published: May 2023

We investigated the role played by lactate and H+ in evoking the exercise pressor reflex in decerebrated rats whose hindlimb muscles were either freely perfused or ischemic. Production of lactate and H+ by the contracting hindlimb muscles was manipulated with CRISPR to render the myophosphorylase gene (PYGM) non-functional with respect to its ability metabolize glycogen to glucose. Three groups of rats were studied, namely those in which both alleles of the myophosphorylase gene was non-functional (MYO -/-; n=6), one allele of the myophosphorylase gene was non-functional (MYO +/-; n=11), and those in which both alleles were functional MYO +/+ (n=11). The exercise pressor reflex was evoked by statically contracting the triceps surae muscles for 30s with or without the femoral artery occluded, the latter rendering the contracting muscles ischemic. The sensitivity of the muscle mechanoreflex was evaluated in each group of rats by passively stretching the triceps surae muscles for 30 seconds. The sensitivity of the muscle metaboreflex was evaluated by injecting lactic acid (24mM, pH=2.4, 100μL) or inorganic phosphate (24mM, pH=6.0, 100 μL) into the arterial supply of the triceps surae muscles. For each contraction, the peak pressor response, the pressor response integrated over the contraction period (i.e., blood pressure index) and the cardioaccelerator response were calculated. Lactate concentrations were measured from arterial blood samples. Static contraction of freely perfused muscles increased blood lactate concentrations in both MYO +/+ rats (1.3 ± 0.8mmol/L; P < 0.001) and MYO +/- rats (0.57 ± 0.41mmol/L; P = 0.030), but not in MYO -/- rats (0.10 ± 0.28mmol/L; P = 0.999). Despite different lactate productions, the peak pressor, the blood pressure index, and the cardioaccelerator responses to freely perfused contraction did not differ between groups (P > 0.32). Compared to contraction with freely perfused hindlimb circulation, static contraction with occluded circulation increased lactate production by 44 ± 40%, and 26 ± 60% in MYO +/+ and MYO +/- rats, respectively, whereas it had no effect on lactate production in MYO-/- rats (-0.05±0.07%). The blood pressure index calculated for ischemic contraction was greater than that calculated for freely perfused contraction in both the MYO +/+ (73 ± 50%; P < 0.001) and the MYO +/- rats (50 ± 51%; p = 0.050) but not in MYO -/- rats (-10 ± 25%; P=0.734). No difference in the pressor response to passive stretch or lactic acid injection was found between groups (P > 0.295). A greater pressor response to injection of inorganic phosphate was detected, however, in MYO -/- rats (44 ± 24 mmHg) compared to those in MYO +/+ (23 ± 12mmHg; P = 0.0271) and in MYO+/- rats (9 ± 5mmHg; P < 0.001). We conclude that lactate and/or hydrogen ion accumulation in contracting myocytes play a key role in evoking the metabolic component of the exercise pressor reflex during ischemic but not during freely perfused contractions. Supported by NIH grants HL 156594 and HL 156513. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.