Key result
Intrapericardial injection of the P2X receptor agonist α,β-meATP increased mean arterial pressure by 24 mmHg, an effect that was enhanced by 58% following opioid receptor blockade with naloxone.
Why the study?
The roles of both P2 receptors and endogenous opioids in cardiac sympathoexcitatory reflex responses during myocardial ischemia remain unclear.
Does activation of cardiac P2X receptors evoke cardiac sympathoexcitatory reflex responses, and are these modulated by endogenous opioids in rats?
Does activation of cardiac P2X receptors evoke cardiac sympathoexcitatory reflex responses, and are these modulated by endogenous opioids in rats?
p-value: p=<0.05
Activation of cardiac P2X2/3 and P2X3 receptors evokes cardiac sympathoexcitatory reflex responses that are suppressed by endogenous opioids in a rat model.
Suggests cardiac P2X receptors mediate opioid-modulated sympathoexcitation in rats; leaves open translation to human cardiovascular reflexes.
Myocardial ischemia evokes powerful reflex responses through activation of vagal and sympathetic afferents in the heart through the release of ischemic metabolites. We have demonstrated that extracellular ATP stimulates cardiac sympathetic afferents through P2 receptor-mediated mechanism, and that opioid peptides suppress these afferents’ activity. However, the roles of both P2 receptor and endogenous opioids in cardiac sympathoexcitatory reflex (CSR) responses remain unclear. We therefore hypothesized that activation of cardiac P2 receptor evokes CSR responses by stimulating cardiac sympathetic afferents and these CSR responses are modulated by endogenous opioids. We observed that intrapericardial injection of α,β-methylene ATP (α,β-meATP, P2X receptor agonist), but not ADP (P2Y receptor agonist), caused a graded increase in mean arterial pressure in rats with sinoaortic denervation and vagotomy. This effect of α,β-meATP was abolished by blockade of cardiac neural transmission with intrapericardial procaine treatment and eliminated by intrapericardial A-317491, a selective P2X 2/3 and P2X 3 receptor antagonist. Intrapericardial α,β-meATP also evoked CSR response in vagus-intact rats. Furthermore, the P2X receptor-mediated CSR responses were enhanced by intrapericardial naloxone, a specific opioid receptor antagonist. These data suggest that stimulation of cardiac P2X 2/3 and P2X 3 , but not P2Y receptors, powerfully evokes CSR responses through activation of cardiac spinal afferents, and that endogenous opioids suppress the P2X receptor-mediated CSR responses.
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Fu et al. (2019) studied Cardiac sympathoexcitatory reflex response. α,β-methylene ATP (α,β-meATP) vs. Vehicle (PBS) or ADP was evaluated on Change in mean arterial pressure (MAP) (p=<0.05). Intrapericardial injection of the P2X receptor agonist α,β-meATP increased mean arterial pressure by 24 mmHg, an effect that was enhanced by 58% following opioid receptor blockade with naloxone.
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