Hypertrophy of intramyocardial arteriolar smooth muscle cells in experimental renal failure

Wall thickening of intramyocardial arteries in patients with chronic renal failure may contribute to the increased susceptibility of the uremic heart to ischemic injury. In this context, the following questions arise: (I) Is intramyocardial wall thickening in experimental renal failure due to hypert rophy, hyperplasia or both? (2) Which stimuli trigger wall thickening? Usin g novel stereologic techniques (Nucleator, Selector), intramyocardial arter ies were examined in sham-operated and subtotally nephrectomized (SNX) Spra gue Dawley rats with moderate renal failure of 8 wk duration. Systolic BP d uring the experiment was not significantly different in both groups. Absolu te and relative left ventricular weight, wall thickness (5.69 +/- 1.11 mu m versus 4.42 +/- 0.99 mu m), and wall-to-lumen ratio of intramyocardial art eries (0.117 +/- 0.03 mu m/mu m versus 0.089 +/- 0.01 mu m/mu m) were signi ficantly greater in SNX than in sham-operated rats. The mean cell and nucle ar volume of intramyocardial arteriolar smooth muscle cells was significant ly increased in SNX rats (650 +/- 230 mu m(3) versus 430 +/- 90 mu m(3) and 26 +/- 4.5 versus 19.9 +/- 2.2 mu m(3) respectively). In parallel, the tot al arteriolar wall volume was significantly greater in the left ventricle o f SNX (+58%) compared with sham rats. In contrast, the total length of all left ventricular arteries was comparable in both groups. The increase in me an cell volume without significant change in cell number indicates that art eriolar wall thickening in the heart of SNX rats is explained by hypertroph y rather than hyperplasia of arterial smooth muscle cells. This finding in a nonhypertensive experimental model of chronic renal failure contrasts wit h findings in spontaneously hypertensive rats. Independent of BP and left V entricular hypertrophy, specific growth signals must act on cardiac arterio lar smooth muscle cells.