Chronic Intermittent Hypoxia-Induced Augmented Cardiorespiratory Outflow Mediated by Vasopressin-V1A Receptor Signaling in the Medulla

  • Kc Prabha
  • Kannan V. Balan
  • Richard J. Martin
  • Joseph C. LaManna
  • Musa A. Haxhiu
  • Thomas E. Dick
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 701)


A co-morbidity of sleep-disordered breathing is hypertension associated with elevated sympathetic nerve activity, which may result fromchronic intermittent hypoxia (CIH). CIH evokes plasticity in cardiorespiratory regulating sites, including the paraventricular nucleus (PVN), which acts to sustain increased sympathetic nerve activity. Our working hypothesis is that vasopressin neurons mediate the sustained increase in blood pressure and altered breathing associated with CIH. In a series of neuroanatomical experiments, we determined if vasopressin-containing PVN neurons innervate rostral ventrolateral medulla (RVLM), and altered cardiorespiratory responses induced by CIH conditioning (8h/day for 10 days) is mediated by vasopressin-V1A receptor signaling in the medulla. In the first set of experiments, cholera toxin β subunit was microinjected into the RVLM to delineate innervation of the PVN. Immunohistochemistry data showed vasopressin-containing PVN neurons were double-labeled with cholera toxin β subunit, indicating vasopressin projection to the RVLM. In the second set, sections of the medulla were immunolabeled for vasopressin V1A receptor, and its expression was significantly higher in the RVLM and in the neighboring rostral ventral respiratory column in CIH- than from RAconditioned rats. In a series of physiological experiments,we determined if blocking the vasopressin V1A receptor in the medulla would normalize blood pressure in CIHconditioned rats and also attenuate the evoked responses to PVN disinhibition.Blood pressure, heart rate, diaphragmatic and genioglossus muscle activity were recorded in anesthetized, ventilated and vagotomized rats. The PVN was disinhibited by microinjecting bicuculline before and after blocking vasopressin V1A receptors in the RVLM/rostral ventral respiratory column. In RA-conditioned rats, PVN disinhibition increased blood pressure, heart rate, minute diaphragmatic and genioglossus muscle activity, and these increases were attenuated after blocking the vasopressin V1A receptor. In CIH-conditioned rats, a significantly greater dose of blocker was required to blunt these physiological responses and it also normalized the baseline blood pressure. Our findings indicate that vasopressin is the neuropeptide released from PVN neurons that modulates cardiorespiratory output via the RVLMand rostral ventral respiratory column.


Obstructive Sleep Apnea Cholera Toxin Sympathetic Nerve Activity Chronic Intermittent Hypoxia Hypothalamic Paraventricular Nucleus 
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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kc Prabha
    • 1
  • Kannan V. Balan
    • 1
  • Richard J. Martin
    • 1
  • Joseph C. LaManna
    • 2
  • Musa A. Haxhiu
    • 1
  • Thomas E. Dick
    • 3
  1. 1.Department of PediatricsCase Western Reserve UniversityClevelandUSA
  2. 2.Department of Physiology and BiophysicsCase Western Reserve UniversityClevelandUSA
  3. 3.Department of MedicineCase Western Reserve UniversityClevelandUSA

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