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American Journal of Pathology, Vol 135, 291-299, Copyright © 1989 by American Society for Investigative Pathology

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Increased deposition of basement membrane macromolecules in specific vessels of the spontaneously hypertensive rat

PG McGuire, DG Brocks, PD Killen and RW Orkin
Developmental Biology Laboratory, Massachusetts General Hospital, Boston.

The genetically determined chronic hypertension manifested in the Spontaneously Hypertensive Rat (SHR) serves as a useful animal model for the study of human essential hypertension. One of the earliest morphologic changes observed in the vasculature of the SHR is the development of a thickened subendothelial space (SES). Neither the biochemical composition nor the anatomic distribution of this early subendothelial deposit has been definitively determined. By combining morphologic, immunologic, and molecular biological approaches, it was demonstrated that by 15 weeks the acellular subendothelial thickening in the vasculature of the SHR results at least in part from the increased synthesis and deposition of basement membrane macromolecules. Moreover, rather than being manifest systemically, this early connective tissue lesion appears to be localized primarily to the aorta and major branches off the aortic arch.