AORTIC CHANGES IN EXPERIMENTAL RENAL-FAILURE - HYPERPLASIA OR HYPERTROPHY OF SMOOTH-MUSCLE CELLS

Cardiovascular complications are a well-known feature of chronic renal failure. Increased wall thickness of intramyocardial arterioles and e lastic (aorta) and peripheral (mesenteric) arteries is seen even after normalization of brood pressure. It is currently unknown whether such increases result from hyperplasia of vascular smooth muscle cells, hy pertrophy, or a combination of both or from an increase in aortic extr acellular matrix. Using a recently developed unbiased stereological te chnique (the dissector), we investigated the aortas of subtotally neph rectomized rats and sham-operated controls after per fusion fixation. We determined aortic wall thickness, cross-sectional area of aortic me dia. total number of vascular smooth muscle cells per unit aortic leng th (1 mm), mean cell and nuclear volumes, volume density of elastic fi bers, extracellular matrix, vascular smooth muscle cells, and total vo lumes of these structures per unit of aortic length (1 mm). Blood pres sure was not significantly increased in subtotally nephrectomized mts. In contrast, wall thickness, cross-sectional media, total number of a ortic vascular smooth muscle cells, and volume of extracellular matrix including collagen were significantly increased after subtotal nephre ctomy, whereas cellular hypertrophy was only modest and an increase in elastic fibers did not occur. In conclusion, increased aortic wall th ickness in experimental renal failure results primarily from an increa se in aortic extracellular matrix. In addition, however, proliferation of aortic vascular smooth muscle cells resulting in cell hyperplasia also contributed to aortic wall thickening to a minor degree. It appea rs that aortic wall thickening is caused by secretory stimulation of t he proliferating vascular smooth muscle cells, resulting in increased matrix production, The nature of the underlying stimulus requires furt her investigation.