Regulation of the endogenous NO pathway by prolonged inhaled NO in rats

Deborah U. Frank, Damian J. Horstman, Geoffrey N. Morris, Roger A. Johns, George F. Rich

Research output: Contribution to journalArticlepeer-review

Abstract

Nitric oxide (NO) modulates the endogenous NO-cGMP pathway. We determined whether prolonged inhaled NO downregulates the NO-cGMP pathway, which may explain clinically observed rebound pulmonary hypertension. Rats were placed in a normoxic (N; 21% O2) or hypoxic (H; 10% O2) environment with and without inhaled NO (20 parts/million) for 1 or 3 wk. Subsequently, nitric oxide synthase (NOS) and soluble guanylate cyclase (GC) activity and endothelial NOS (eNOS) protein levels were measured. Perfusate cGMP levels and endothelium-dependent and -independent vasodilation were determined in isolated lungs. eNOS protein levels and NOS activity were not altered by inhaled NO in N or H rats. GC activity was decreased by 60 ± 10 and 55 ± 11% in N and H rats, respectively, after 1 wk of inhaled NO but was not affected after 3 wk. Inhaled NO had no effect on perfusate cGMP in N lungs. Inhaled NO attenuated the increase in cGMP levels caused by 3 wk of H by 57 ± 11%, but there was no rebound in cGMP after 24 h of recovery. Endothelium- dependent vasodilation was not altered, and endothelium-independent vasodilation was not altered (N) or slightly increased (H, 10 ± 3%) by prolonged inhaled NO. In conclusion, inhaled NO did not alter the endogenous NO-cGMP pathway as determined by eNOS protein levels, NOS activity, or endothelium-dependent vasodilation under N and H conditions. GC activity was decreased after 1 wk; however, GC activity was not altered by 3 wk of inhaled NO and endothelium-independent vasodilation was not decreased.

Original languageEnglish (US)
Pages (from-to)1070-1078
Number of pages9
JournalJournal of applied physiology
Volume85
Issue number3
DOIs
StatePublished - Sep 1998
Externally publishedYes

Keywords

  • Chronic hypoxia
  • Cyclic 3',5'-guanosine monophosphate
  • Guanylate cyclase
  • Nitric oxide
  • Nitric oxide synthase
  • Pulmonary hypertension
  • Pulmonary vasodilation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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