Effects of chronic pulmonary overcirculation on pulmonary vasomotor tone. Ann Thorac Surg 1999 Feb;67(2):522-7
Date
04/10/1999Pubmed ID
10197682DOI
10.1016/s0003-4975(98)01141-2Scopus ID
2-s2.0-0032929882 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
BACKGROUND: A model of shunt-induced pulmonary hypertension was used to study the effects of pulmonary overcirculation on endothelial nitric oxide synthase (eNOS) and cytochrome P450-4A (cP450-4A) vasodilatory mechanisms and related hemodynamic responses.
METHODS: An aortopulmonary shunt was constructed in 6-week-old piglets (n = 7, sham-operated controls n = 8). Hemodynamic measurements were made 4 weeks later under serial experimental conditions: baseline (fractional concentration of oxygen, 0.4); inhaled nitric oxide, 25 ppm (INO); hypoxia (fractional concentration of oxygen, 0.14); hypoxia + INO; N(omega)-nitro-L-arginine methylester (L-NAME 30 mg/kg intravenously, competitive NOS inhibitor); and L-NAME + INO. Lung protein levels of eNOS and cP450-4A and NOS activity were compared between groups.
RESULTS: Shunted animals had a higher baseline pulmonary artery pressure (p < 0.05). L-NAME resulted in a greater increase in pulmonary vascular resistance in shunted animals (150% +/- 26% shunt versus 69% +/- 14% control; p = 0.01). The INO administered during baseline conditions decreased pulmonary vascular resistance only in control animals (p < 0.05). Protein levels of eNOS and NOS activity were similar in both groups; however, cP450-4A protein levels were decreased in the shunted group (p = 0.02).
CONCLUSIONS: The NO production was preserved in shunted animals but they demonstrated greater vasodilatory dependence on NO, evidenced by an exaggerated increase in pulmonary vascular resistance after NOS inhibition. Loss of the cP450-4A vasodilatory system may be the driving force for NO dependency in the shunted pulmonary circulation.
Author List
Parviz M, Bousamra M 2nd, Chammas JH, Birks EK, Presberg KW, Jacobs ER, Nelin LDAuthor
Kenneth W. Presberg MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCytochrome P-450 CYP4A
Cytochrome P-450 Enzyme System
Endothelium, Vascular
Hemodynamics
Hypertension, Pulmonary
Mixed Function Oxygenases
Nitric Oxide Synthase
Pulmonary Artery
Pulmonary Wedge Pressure
Swine
Vascular Resistance
Vasomotor System
