Hypertrophy of Intramyocardial Arteriolar Smooth Muscle Cells in Experimental Renal Failure

Abstract

Abstract. 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: (1) Is intramyocardial wall thickening in experimental renal failure due to hypertrophy, hyperplasia or both? (2) Which stimuli trigger wall thickening? Using novel stereologic techniques (Nucleator, Selector), intramyocardial arteries were examined in sham-operated and subtotally nephrectomized (SNX) Sprague Dawley rats with moderate renal failure of 8 wk duration. Systolic BP during the experiment was not significantly different in both groups. Absolute and relative left ventricular weight, wall thickness (5.69 ± 1.11 μm versus 4.42 ± 0.99 μm), and wall-to-lumen ratio of intramyocardial arteries (0.117 ± 0.03 μm/μm versus 0.089 ± 0.01 μm/μm) were significantly greater in SNX than in sham-operated rats. The mean cell and nuclear volume of intramyocardial arteriolar smooth muscle cells was significantly increased in SNX rats (650 ± 230 μm3versus 430 ± 90 μm3 and 26 ± 4.5 versus 19.9 ± 2.2 μm3, respectively). In parallel, the total arteriolar wall volume was significantly greater in the left ventricle of SNX (+ 58%) compared with sham rats. In contrast, the total length of all left ventricular arteries was comparable in both groups. The increase in mean cell volume without significant change in cell number indicates that arteriolar wall thickening in the heart of SNX rats is explained by hypertrophy rather than hyperplasia of arterial smooth muscle cells. This finding in a nonhypertensive experimental model of chronic renal failure contrasts with findings in spontaneously hypertensive rats. Independent of BP and left ventricular hypertrophy, specific growth signals must act on cardiac arteriolar smooth muscle cells.