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Urotensin II promotes vagal‐mediated bradycardia by activating cardiac‐projecting parasympathetic neurons of nucleus ambiguus
Author(s) -
Brailoiu Gabriela Cristina,
Deliu Elena,
Rabinowitz Joseph E.,
Tilley Douglas G.,
Koch Walter J.,
Brailoiu Eugen
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12679
Subject(s) - nucleus ambiguus , parasympathetic nervous system , bradycardia , vagus nerve , chemistry , medicine , neuroscience , autonomic nervous system , biology , heart rate , central nervous system , medulla oblongata , blood pressure , stimulation
Urotensin II (U‐ II ) is a cyclic undecapeptide that regulates cardiovascular function at central and peripheral sites. The functional role of U‐ II nucleus ambiguus, a key site controlling cardiac tone, has not been established, despite the identification of U‐ II and its receptor at this level. We report here that U‐ II produces an increase in cytosolic Ca 2+ concentration in retrogradely labeled cardiac vagal neurons of nucleus ambiguus via two pathways: (i) Ca 2+ release from the endoplasmic reticulum via inositol 1,4,5‐trisphosphate receptor; and (ii) Ca 2+ influx through P/Q‐type Ca 2+ channels. In addition, U‐ II depolarizes cultured cardiac parasympathetic neurons. Microinjection of increasing concentrations of U‐ II into nucleus ambiguus elicits dose‐dependent bradycardia in conscious rats, indicating the in vivo activation of the cholinergic pathway controlling the heart rate. Both the in vitro and in vivo effects were abolished by the urotensin receptor antagonist, urantide. Our findings suggest that, in addition, to the previously reported increase in sympathetic outflow, U‐ II activates cardiac vagal neurons of nucleus ambiguus, which may contribute to cardioprotection. Our study characterizes the effects of urotensin II (U‐II) on cardiac‐projecting nucleus ambiguus neurons. U‐II depolarizes these neurons, promotes Ca 2+ entry via P/Q‐type Ca 2+ channels and Ca 2+ release from the endoplasmic reticulum via inositol 1,4,5‐trisphosphate receptors. U‐II microinjection into the nucleus ambiguus elicits bradycardia in conscious rats. Thus, U‐II increases cardiac vagal tone, potentially promoting cardioprotection, as previously reported.