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

• Published in: Journal of applied physiology (1985) Vol. 85; no. 3; pp. 1070 - 1078
• Main Authors: Frank, Deborah U, Horstman, Damian J, Morris, Geoffrey N, Johns, Roger A, Rich, George F
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.09.1998; American Physiological Society
• Subjects: Administration, Inhalation; Anatomy & physiology; Animals; Biological and medical sciences; Blotting, Western; Chromatography, Gas; Cyclic GMP - physiology; Endothelium, Vascular - physiology; Gases; Guanylate Cyclase - antagonists & inhibitors; Guanylate Cyclase - metabolism; Hypertension; Hypoxia - physiopathology; In Vitro Techniques; Male; Medical sciences; Nitric Oxide - administration & dosage; Nitric Oxide - pharmacology; Nitric Oxide - physiology; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type III; Pneumology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Rats; Rats, Sprague-Dawley; Respiratory system; Rodents; Signal Transduction - drug effects; Signal Transduction - physiology; Vasodilation - drug effects; Vasodilation - physiology; Animal model; Oxygen; Rat; Respiratory disease; Enzyme; Rodentia; Cardiovascular disease; Environmental factor; 3',5'-GMP; Metabolic pathway; Pulmonary hypertension; Nitric-oxide synthase; Vertebrata; Chronic; Regulation(control); Mammalia; Animal; Nitric oxide; Hypoxia; Oxidoreductases
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1998.85.3.1070

Departments of 1  Biomedical Engineering and 2  Anesthesiology, University of Virginia Health System, Charlottesville, Virginia 22906-0010 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% O 2 ) or hypoxic (H; 10% O 2 ) 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. nitric oxide; pulmonary hypertension; chronic hypoxia; nitric oxide synthase; guanylate cyclase; cyclic 3',5'-guanosine monophosphate; pulmonary vasodilation