Role of nitric oxide-containing factors in the ventilatory and cardiovascular responses elicited by hypoxic challenge in isoflurane-anesthetized rats

J Appl Physiol (1985). 2014 Jun 1;116(11):1371-81. doi: 10.1152/japplphysiol.00842.2013. Epub 2014 Apr 17.

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.

Keywords: cardiovascular; frequency of breathing; hypoxia; isoflurane-anesthetized rats; nitric oxide factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Anesthetics, Inhalation / administration & dosage
  • Animals
  • Blood Pressure / drug effects*
  • Heart Rate / drug effects*
  • Hypoxia / physiopathology*
  • Isoflurane / administration & dosage*
  • Male
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Rate / drug effects*

Substances

  • Anesthetics, Inhalation
  • Nitric Oxide
  • Isoflurane