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Hypercapnia attenuates intermittent hypoxia‐induced pulmonary hypertension
Author(s) -
Norton Charles Elbert,
Snow Jessica B.,
Kanagy Nancy L.,
Walker Benjimen R.,
Resta Thomas C.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1436-b
Subject(s) - hypercapnia , hypoxic pulmonary vasoconstriction , hypoxia (environmental) , vasoconstriction , medicine , right ventricular hypertrophy , pulmonary hypertension , intermittent hypoxia , cardiology , anesthesia , endocrinology , acidosis , chemistry , obstructive sleep apnea , oxygen , organic chemistry
Sleep apnea with resultant exposure to intermittent hypoxia/hypercapnia (IHHC) is characterized by pulmonary hypertension (PH) and right ventricle (RV) hypertrophy similar to that observed with chronic sustained hypoxia (CH). However, CH‐induced PH, associated with enhanced vasoconstrictor reactivity, polycythemia and arterial remodeling, is inhibited by chronic hypercapnia. We therefore hypothesized that hypercapnia coincident with intermittent hypoxia (IH) similarly inhibits increases in agonist‐mediated pulmonary vasoconstriction and PH. To test this hypothesis, we compared vasoconstrictor responses to the thromboxane analog U‐46619 in isolated, saline‐perfused lungs from rats exposed to IH (3 min cycles of 5% O2/air flush), IHHC (3 min cycles of 5% O2, 5% CO2/air flush) or air (air/air cycling) for 7 hr/day for 2 wk. Hematocrit, arterial wall thickness and the ratio of RV to total ventricle weight were measured as indices of polycythemia, arterial remodeling and PH, respectively. Consistent with our hypothesis, hypercapnia prevented IH‐induced polycythemia, vascular remodeling and RV hypertrophy. However, IH and IHHC similarly augmented vasoconstriction to U‐46619. We conclude that hypercapnia protects against IH‐induced PH. In contrast, increases in pulmonary vasoconstrictor reactivity following IH are unaltered by combined exposure with hypercapnia.