title: Role of nitric oxide-containing factors in the ventilatory and cardiovascular responses elicited by hypoxic challenge in isoflurane-anesthetized rats.
abstract: Exposure to hypoxia elicits changes in mean arterial blood pressure (MAP), heart rate, and frequency of breathing (fR). The objective of this study was to determine the role of nitric oxide (NO) in the cardiovascular and ventilatory responses elicited by brief exposures to hypoxia in isoflurane-anesthetized rats. The rats were instrumented to record MAP, heart rate, and fR and then exposed to 90 s episodes of hypoxia (10% O2, 90% N2) before and after injection of vehicle, the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), or the inactive enantiomer D-NAME (both at 50 μmol/kg iv). Each episode of hypoxia elicited a decrease in MAP, bidirectional changes in heart rate (initial increase and then a decrease), and an increase in fR. These responses were similar before and after injection of vehicle or D-NAME. In contrast, the hypoxia-induced decreases in MAP were attenuated after administration of L-NAME. The initial increases in heart rate during hypoxia were amplified whereas the subsequent decreases in heart rate were attenuated in L-NAME-treated rats. Finally, the hypoxia-induced increases in fR were virtually identical before and after administration of L-NAME. These findings suggest that NO factors play a vital role in the expression of the cardiovascular but not the ventilatory responses elicited by brief episodes of hypoxia in isoflurane-anesthetized rats. Based on existing evidence that NO factors play a vital role in carotid body and central responses to hypoxia in conscious rats, our findings raise the novel possibility that isoflurane blunts this NO-dependent signaling.
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia;
authors.forename: James P
authors.initials: JP
authors.lastname: Mendoza
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia;
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Passafaro
authors.affiliation: Division of Biology, Galleon Pharmaceuticals, Horsham, Pennsylvania;
authors.forename: Santhosh M
authors.initials: SM
authors.lastname: Baby
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia;
authors.forename: Alex P
authors.initials: AP
authors.lastname: Young
authors.affiliation: Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, Iowa; and.
authors.forename: James N
authors.initials: JN
authors.lastname: Bates
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, Virginia;
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gaston
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio sjl78@case.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D000860:Hypoxia / Q000503:physiopathology*; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056152:Respiratory Rate / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D009569:Nitric Oxide; D007530:Isoflurane
keywords: cardiovascular; frequency of breathing; hypoxia; isoflurane-anesthetized rats; nitric oxide factors
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