TEMPORAL ALTERATIONS IN SPECIFIC BASEMENT-MEMBRANE COMPONENTS IN LUNGS FROM MONOCROTALINE-TREATED RATS

The present study utilized the monocrotaline (MCT) model of pulmonary hypertension in rats to examine temporal alterations in steady-state l evels of basement membrane (BM) component mRNA and deposition of prote in using Northern analysis and immunohistochemistry, respectively. MCT (60 mg/kg, subcutaneous) produced sustained increases in lung dry tis sue mass by 7 days, right ventricular mass by 14 days, and pulmonary a rterial pressure by 21 days after administration. mRNA levels specific for laminin (LM) were elevated as early as 1 day after MCT treatment, while mRNA for all BM components examined except type IV collagen wer e increased in lungs from MCT-treated rats by day 4. Differences in LM , perle-can (PN), and type IV collagen-specific mRNAs from lung tissue between MCT-treated and control rats disappeared by day 14. In contra st, fibronectin (FN) mRNA remained elevated in lung tissue from MCT-tr eated rats from day 4 onward. Increases in immunolocalizable FN and LM in the vasculature, and PN and type IV collagen in gas exchange areas , were observed 4 days after MCT treatment compared with controls. The se changes generally became more pronounced by 21 days after MCT admin istration, at which time the parenchyma of MCT-treated rats also demon strated increases in immunolocalizable FN, LM, and BM-chondroitin sulf ate proteoglycan (BM-CSPG). The pulmonary vasculature additionally sho wed increases in type IV collagen, PN, and BM-CSPG in MCT-treated rats compared with controls by 21 days. These observations suggest that th e accumulation of specific BM components in the pulmonary vasculature and parenchyma may contribute to the pathogenesis and maintenance of M CT-induced hypertensive pulmonary vascular disease.