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Impaired autonomic cardiac regulation due to altered baroreceptor reflex sensitivity in conscious P2rX7 knockout rats
Author(s) -
Kuzmin Vladislav S,
Potter D'Anna L,
Arkhipov Sergey N,
Pavlov Tengis S
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.558.2
Subject(s) - baroreceptor , baroreflex , medicine , reflex , heart rate , blood pressure , atropine , carotid sinus , endocrinology , reflex bradycardia , cardiology , autonomic nervous system , anesthesia
Baroreceptor (BR) reflex is a central mechanism that underlies autonomic control of the circulation due to tight coordination between heart output and peripheral vasculature resistance. Abnormal and/or pathological sensitivity of the BR reflex (BRRS) is associated with many cardiovascular diseases. ATP acting as a co‐transmitter in sympathetic and parasympathetic terminals regulates excitability of the carotid sinus cells and therefore participates in BRR. The goal of the present study was to reveal the role of P2X7 receptors in the autonomic control of the cardiovascular system and BR reflex sensitivity. Method We used a constitutive CRISPR/Cas9‐mediated knockout of P2X7 receptor in the PCK rat background. PCK rats are a model of chronic autosomal recessive polycystic kidney disease which associated with cardiovascular complications. As PCK rats were originally derived from the Sprague Dawley strain, the latter was used as control. BRR was studied in vivo in a series of telemetry‐based subchronic experiments. DSI HD‐S11 transmitters were implanted for direct blood pressure collection from carotid artery in addition to lead II electrode placement for electrocardiogram. After a week‐long recovery period standard approach for BRR testing with bolus intravenous sodium nitroprusside (SNP 10μg/kg) injection was used before and after double autonomic blockade (DAB, atropine plus atenolol). Mean arterial pressure (MAP) and heart rate (HR) were collected from free‐moving conscious animals and BRRS was calculated as ΔMAP/ΔHR relation. Results No significant difference in resting HR was observed in Sprague‐Dawley (SD) and WT or P2X7 KO PCK rats (378±15, n=6; 359±16, n=6 and 365±8, n=6 respectively). After DAB, HR reduction was similar in WT and KO groups (11.3±2.2% and 10.1±2.3%), but SD demonstrated a more pronounced effect (18.2±3.1%). The KO rats demonstrated significantly reduced BRRS in comparison to WT and SD animals (0.43±0.05 and 0.63±0.07, 0.57±0.06, respectively). Moreover, while SD and WT rats are characterized by negative slope of ΔMAP‐ΔHR relation, ΔHR in KO group demonstrates lack of dependence on ΔMAP. In addition, the time from the beginning to maximal HR elevation in response to SNP application was significantly shorter in KO (13.5±2.5 s) vs SD (32.4±3.6s). Conclusion Autonomic control of cardiac function in PCK rats is impaired in comparison to SD rats due to chronic kidney disease. P2X7 deficiency leads to impaired BR reflex sensitivity. P2X7 receptors involved in neurotransmission contribute to the sympathetic/parasympathetic balance of cardiac function control. Support or Funding Information NIH R00 DK105160, P30 DK090868 via Baltimore PKD Center P&F Grant and APS Dean Franklin Award This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .