Immunohistochemical Localization of Extracellular Matrix Proteins in Cerebral Vessels in Chronic Hypertension

Vascular hypertrophy or vascular remodeling are both associated with an increase in the extracellular matrix of cerebral arteries and arterioles in chronic hypertension. Rats with chronic renal hypertension were studied to determine whether the extracellular matrix proteins--collagen IV, laminin, and fibronectin--are increased in the thick-walled cerebral vessels in brain and those associated with areas of blood-brain barrier (BBB) breakdown to protein. The latter was detected by extravasation of endogenous serum proteins in brain. Serum proteins and the extracellular matrix proteins--fibronectin, laminin, and collagen IV--were detected by immunohistochemistry. Hypertensive rats having blood pressures over 150 mm Hg showed mild to moderate degrees of mural thickening of pial and intracerebral arterioles. In addition, these vessels demonstrated increased immunoreactivity with collagen IV, fibronectin, and laminin antisera. This occurred concomitant with the development of hypertension and prior to the observation of BBB breakdown to protein. Four rats having mean maximum systolic blood pressures in excess of 220 mm Hg developed multifocal areas of increased vascular permeability to endogenous serum proteins in the boundary zones of the territories supplied by the major cerebral arteries. The arterioles in these areas showed a severe degree of vascular thickening, which was due to medial hyperplasia/hypertrophy and increased mural deposition of serum proteins and the extracellular matrix proteins--laminin, fibronectin, and collagen IV. This study demonstrates that extracellular matrix proteins play an important role in the vascular response to increased intraluminal pressure. However, since this change occurs in diseases in the absence of hypertension it should be regarded as a nonspecific response of cellular components of vessel walls to injury.