Chemogenetic inhibition of NTS astrocytes normalizes cardiac autonomic control and ameliorate hypertension during chronic intermittent hypoxia
Pereyra, Katherin
Pontificia Universidad Catolica de Chile
Heras, Alexandra Las
Pontificia Universidad Catolica de Chile
Toledo, Camilo
Pontificia Universidad Catolica de Chile
Diaz-Jara, Esteban
Pontificia Universidad Catolica de Chile
Iturriaga, Rodrigo
Pontificia Universidad Catolica de Chile
Del Rio, Rodrigo
Journal
Biological Research
ISSN
0716-9760
0717-6287
Open Access
gold
Volume
56
BackgroundObstructive sleep apnea (OSA) is characterized by recurrent episodes of chronic intermittent hypoxia (CIH), which has been linked to the development of sympathoexcitation and hypertension. Furthermore, it has been shown that CIH induced inflammation and neuronal hyperactivation in the nucleus of the solitary tract (NTS), a key brainstem region involved in sympathetic and cardiovascular regulation. Since several studies have proposed that NTS astrocytes may mediate neuroinflammation, we aimed to determine the potential contribution of NTS-astrocytes on the pathogenesis of CIH-induced hypertension.ResultsTwenty-one days of CIH induced autonomic imbalance and hypertension in rats. Notably, acute chemogenetic inhibition (CNO) of medullary NTS astrocytes using Designer Receptors Exclusively Activated by Designers Drugs (DREADD) restored normal cardiac variability (LF/HF: 1.1 +/- 0.2 vs. 2.4 +/- 0.2 vs. 1.4 +/- 0.3, Sham vs. CIH vs. CIH + CNO, respectively) and markedly reduced arterial blood pressure in rats exposed to CIH (MABP: 82.7 +/- 1.2 vs. 104.8 +/- 4.4 vs. 89.6 +/- 0.9 mmHg, Sham vs. CIH vs. CIH + CNO, respectively). In addition, the potentiated sympathoexcitation elicit by acute hypoxic chemoreflex activation in rats exposed to CIH was also completely abolished by chemogenetic inhibition of NTS astrocytes using DREADDs.ConclusionOur results support a role for NTS astrocytes in the maintenance of heightened sympathetic drive and hypertension during chronic exposure to intermittent hypoxia mimicking OSA.
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