The three to four fold greater incidence of primary pulmonary hypertension in women when compared with men indicates the possible existence of a prominent sexual dimorphism in the vascular tissue of the lung. Primary pulmonary hypertension is generally manifest after puberty which also indicates a possible hormonal basis for the disease. Insight into the disease can be obtained by determining the presence of sexual dimorphism in the sensitivity and contractility of the pulmonary vasculature and relating this to the role of the endothelium which is recognized to release both contractile and relaxing factors. Preliminary studies indicate that this is a practical approach and have yielded results which indicate marked sexual differences in the response of vascular segments of the main pulmonary artery of the rat which relate to both the endothelium and the vascular smooth muscle.
The specific aims of this proposal are to establish in immature, mature and older rats the degree of expression of this sexual dimorphism, to identify the contributions of the endothelium and the vascular smooth muscle to the tension generated and to determine the effect of endocrinological manipulation in order to identify the specific hormonal basis. This will be done by tension and sensitivity measurements of rat pulmonary artery vessel segments under isometric conditions in vascular preparations where the endothelium is intact and where it is removed. Pilot experiments indicate that the dimorphism is best expressed by oxidation products of arachidonate. This will be evaluated with selected eicosanoids and other spasmogens including leukotrienes which are found in large amounts in pulmonary vessels. These data will provide an endocrinological basis for studies in perfused lung models. The long-term objective is to provide endocrinological insight into possible causes of primary pulmonary hypertension.
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