COARCTATION INDUCES ALTERATIONS IN BASEMENT-MEMBRANES IN THE CARDIOVASCULAR-SYSTEM

A coarctation hypertensive rat model was used to examine the effects o f elevated blood pressure on basement membrane component synthesis by cardiac myocytes and aorta using immunohistochemistry and Northern blo t analysis. Carotid arterial pressure increased immediately on coarcta tion, and left ventricular hypertrophy was maximal within 5 days. In i mmunohistochemical studies, fibronectin and laminin were increased and the basement membrane chondroitin sulfate proteoglycan decreased in b oth the subendothelial space and smooth muscle cell basement membranes of the aorta above the clip compared with controls, whereas only fibr onectin was elevated in the aorta below the clip. No change in basemen t membrane staining intensity for the cardiac myocytes was observed. A lterations in steady-state mRNA levels for fibronectin and laminin in the aorta paralleled those observed by immunohistochemical analysis wi th regard to protein and tissue type affected as well as intensity of the changes. However, changes in mRNA levels (but not protein depositi on) for perlecan and type IV collagen were also observed in aortas fro m hypertensive rats compared with controls. Increases in steady-state mRNA levels for all basement membrane components in the heart and vasc ulature peaked before maximal cardiac hypertrophy (5 days). These stud ies indicate that alterations in basement membrane component depositio n in the hypertrophied vasculature occur at both transcriptional and t ranslational levels and suggest that the cell attachment glycoproteins fibronectin and laminin may be important factors in the vascular resp onse to elevated transmural pressure.