MECHANICS OF PULMONARY VASCULAR SMOOTH MUSCLE

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The long term goal of this proposal is to understand changes that occur in the function of vascular smooth muscle in pulmonary hypertension (PH). The basic mechanical properties of isolated vessels will be studied in normal rats and those with pulmonary hypertension induced by chronic exposure to hypobaric hypoxia. Hypoxic induced PH is characterized by extensive vascular remodeling including increased amounts of smooth muscle, extension of that muscle peripherally and increases in connective tissue. The increased resistance is a function of increased passive wall stiffness and altered smooth muscle contractile function. This proposal will characterize the properties of the smooth muscle cells of pulmonary arterial and venous vessels from normal and hypertensive rats. Circumference: tension and force: velocity relationships will be determined and related to contractile protein content and morphologic characteristics. Maximal active stress will be determined and related to the amount of actin and myosin. This basic characterization will be completed on large and small vessels from both arterial and venous system. In addition, single pulmonary vascular smooth muscle cells will be isolated and studied independent of the vessel wall and surrounding cells. The dependence of pharmacologic response of pulmonary vessels on circumference will be assessed. This proposal will provide unique data concerning the properties of pulmonary vascular smooth muscle in the normal as well as hypertensive vascular bed. This type of characterization will provide insight into the function of this circulation and changes responsible for the development of pulmonary hypertension.