4.3 Article

Effect of knockout of the ASIC3 on cardiovascular reflexes arising from hindlimb muscle in decerebrated rats

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00148.2019

Keywords

APETx2; exercise pressor reflex; mechanoreceptor reflex; metaboreceptor reflex; protons

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Funding

  1. National Institutes of Health [R01-AR059397, P01-HL-134609]

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The exercise pressor reflex is initiated by the contraction-induced activation of group In and IV muscle afferents. The reflex is manifested by increases in arterial blood pressure and cardiac output, which, in turn, are generated by increases in the sympathetic outflow to the heart and vasculature and decreases in the vagal outflow to the heart. In previous experiments. we used a pharmacological approach to assess the role played by the acid-sensing ion channel 3 (ASIC3) on group III and IV afferents in evoking the exercise pressor reflex. In the present experiments, we used an alternative approach, namely functional knockout (KO) of the ASIC3 gene, to confirm and extend our previous finding that pharmacological blockade of the ASIC3 had only a small impact on the expression of the exercise pressor reflex when the arterial supply to the contracting hindlimb muscles of rats was patent. Using this alternative approach, we compared the magnitude of the exercise pressor reflex evoked in ASIC3 KO rats with that evoked in their wild-type (WT) counterparts. We found both WT and ASIC3 KO rats displayed similar pressor responses to static contraction (WT, n = 10, +12 +/- 2 mmHg; KO, n = 9, +11 +/- 2 mmHg) and calcaneal tendon stretch (WT, n = 9, +13 +/- 2 mmHg; KO, n = 7, +11 +/- 2 mmHg). Likewise, both WT and ASIC3 KO displayed similar pressor responses to intra-arterial injection of 12 mM lactic acid (WT, n = 9, +14 +/- 3 mmHg; KO, n = 8, +18 +/- 5 mmHg), 24 mM lactic acid (WT, n = 9, +24 +/- 2 mmHg; KO, n = 8, +20 +/- 5 mmHg), capsaicin (WT, n = 9, +27 +/- 5 mmHg; KO, n = 10, +29 +/- 5 mmHg), and diprotonated phosphate (H2PO4-; WT, n = 6, +22 +/- 3 mmHg; KO, n = 6, +32 +/- 6 mmHg). We conclude that redundant receptors are responsible for evoking the pressor reflexes arising from group III and IV afferents.

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