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a1‐adrenergic Receptor Activation is Necessary for in vivo Hypoglossal Long‐Term Facilitation Following Intermittent Hypoxia in Rats
Author(s) -
Nashold Lisa J,
Neverova Natalia V,
Saywell Shane A,
Feldman Jack L,
Mitchell Gordon S
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.21.6.a1291-a
Respiratory long‐term facilitation (LTF) is a long‐lasting increase in respiratory motor output following intermittent hypoxia (IH). LTF requires intermittent serotonin (5‐HT2A) receptor activation. Since α 1 ‐adrenergic and 5‐HT2A receptors signal through the same G protein (G α q ), we tested the hypothesis that α 1 ‐receptor activation is also required for LTF in hypoglossal (XII) motor output. Four groups of anesthetized, paralyzed, vagotomized and ventilated male Sprague Dawley rats were studied (n=3 per group): IH after pre‐treatment with prazosin (150 μg/kg, iv), an α 1 ‐adrenergic receptor antagonist; IH after blood withdrawal, reducing blood pressure to match prazosin treated rats; IH in untreated rats; and prazosin time control rats without hypoxia. Similar XII LTF was observed in untreated (177 +/− 26% of baseline; p < 0.001) and blood pressure control rats (213 +/− 25%; p < 0.001). No XII LTF was observed in rats pretreated with prazosin (87 +/− 17%; p < 0.001 relative to untreated or time control rats.) The requirement for both 5HT2A and α 1 ‐receptor activation suggests common mechanisms elicited by descending serotonergic and noradrenergic neurons, respectively. The common link may be PKC activation via the Gα q ‐PLC signaling pathway shared by both receptors. Supported by HL07654, HL80209, NS24742, and Roman Reed Spinal Cord Injury Research Fund of California.