Hypothalamic OXT (Oxytocin) Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea

Authors

Jeannette Rodriguez, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Joan B. Escobar, Department of Pharmacology and Physiology, The George Washington University. (J.B.E., E.C.C., J.D., D.M.).
Emily C. Cheung, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Grant Kowalik, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Rebekah Russo, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Jhansi Dyavanapalli, Department of Pharmacology and Physiology, The George Washington University. (J.B.E., E.C.C., J.D., D.M.).
Bridget R. Alber, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Grey Harral, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Aman Gill, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Makeda Melkie, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
Vivek Jain, Department of Medicine, The George Washington University. (V.J.).
Kathryn J. Schunke, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).
David Mendelowitz, Department of Pharmacology and Physiology, The George Washington University. (J.B.E., E.C.C., J.D., D.M.).
Matthew W. Kay, Department of Biomedical Engineering, The George Washington University. (J.R., E.C.C., G.K., R.R., B.R.A., G.H., A.G., M.M., K.J.S., M.W.K.).

Document Type

Journal Article

Publication Date

2-16-2023

Journal

Hypertension (Dallas, Tex. : 1979)

DOI

10.1161/HYPERTENSIONAHA.122.20149

Keywords

blood pressure; hypertension; hypothalamus; hypoxia; oxytocin; transcriptome

Abstract

BACKGROUND: Obstructive sleep apnea is a prevalent and poorly treated cardiovascular disease that leads to hypertension and autonomic imbalance. Recent studies that restore cardiac parasympathetic tone using selective activation of hypothalamic OXT (oxytocin) neurons have shown beneficial cardiovascular outcomes in animal models of cardiovascular disease. This study aimed to determine if chemogenetic activation of hypothalamic OXT neurons in animals with existing obstructive sleep apnea-induced hypertension would reverse or blunt the progression of autonomic and cardiovascular dysfunction. METHODS: Two groups of rats were exposed to chronic intermittent hypoxia (CIH), a model of obstructive sleep apnea, for 4 weeks to induce hypertension. During an additional 4 weeks of exposure to CIH, 1 group was treated with selective activation of hypothalamic OXT neurons while the other group was untreated. RESULTS: Hypertensive animals exposed to CIH and treated with daily hypothalamic OXT neuron activation had lower blood pressure, faster heart rate recovery times after exercise, and improved indices of cardiac function compared with untreated hypertensive animals. Microarray analysis suggested that, compared with treated animals, untreated animals had gene expression profiles associated with cellular stress response activation, hypoxia-inducible factor stabilization, and myocardial extracellular matrix remodeling and fibrosis. CONCLUSIONS: In animals already presenting with CIH-induced hypertension, chronic activation of hypothalamic OXT neurons blunted the progression of hypertension and conferred cardioprotection after an additional 4 weeks of CIH exposure. These results have significant clinical translation for the treatment of cardiovascular disease in patients with obstructive sleep apnea.

APA Citation

Rodriguez, Jeannette; Escobar, Joan B.; Cheung, Emily C.; Kowalik, Grant; Russo, Rebekah; Dyavanapalli, Jhansi; Alber, Bridget R.; Harral, Grey; Gill, Aman; Melkie, Makeda; Jain, Vivek; Schunke, Kathryn J.; Mendelowitz, David; and Kay, Matthew W., "Hypothalamic OXT (Oxytocin) Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea" (2023). GW Authored Works. Paper 2392.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2392

Department

Pharmacology and Physiology