Endothelin induced collagen remodeling in experimental pulmonary hypertension

To investigate pathophysiological roles of endothelin-1 (ET-1) in collagen remodeling in pulmonary hypertension, we measured: (a) mRNA expression, concentration, localization of ET-1; (b) changes in types and content of collagen in the lung; (c) and confirmed direct effects of ET-1 on type V collagen metabolism in vascular smooth muscle cells. Monocrotaline-treated rats showed pulmonary hypertension with medial hypertrophy and perivascular fibrosis of pulmonary arteries. At the progressive stage of pulmonary hypertension, both ET-1 levels and its mRNA expression in the lung increased. Total collagen in the lung rose markedly with a higher rate of increase in type V collagen. ET-1, which exists in vascular smooth muscle cells, other perivascular cells and endothelium, stimulated type V collagen production. Our results suggest that local production of ET-1 in the lung contributes to progression of pulmonary hypertension through changes in phenotypes and content of collagen.