Chronic hypoxia causes remodeling of the pulmonary arterial but not the venous tree. Specific restructuring involves thickening of the arterial walls by hypertrophy and hyperplasia of pulmonary arterial smooth muscle (PASM) and deposition of excess connective tissue. The overall objective of the proposed interdisciplinary project (biochemistry, biophysics, and cell physiology) is to quantitate cellular and functional changes in PASM that occur in response to hypoxia-induced hypertension. This investigation will test the following hypothesis: hypoxia-induced pulmonary hypertension alters pulmonary arterial smooth muscle function by causing hypertrophy and hyperplasia, accompanied by a shift from predominantly contractile towards a more synthetic smooth muscle cell population.
Specific aims of the four year proposed project will determine whether hypoxia-induced pulmonary hypertension: 1): alters maximum shortening ability, 2) alters maximum velocity of shortening, 3) results in changes in maximum isometric tension development, 4) changes relaxation rates, 5) changes reactivity and responsiveness, nad 6) causes shifts in myosin isoform pattern in PASM. Young adult rats (250-275 g) will be made hypoxic by experimentally lowering the percent inspired oxygen to 10%. A combination of biochemical and biophysical techniques will be used in this investigation. the importance of this research is threefold. First, this investigation will provide new basic information of the biophysical properties of PASM that correlates cellular changes with altered function occurring in response to hypoxia-induced pulmonary hypertension. Second, new information elucidating the contribution that PASM plays in the maintenance of hypoxia- induced pulmonary hypertension will be provided. Third, this investigation will generate fundamental knowledge concerning smooth function of the pulmonary artery. Results of this investigation will permit exploration of new therapeutic approaches in the treatment of hypoxia-induced pulmonary hypertension.
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