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Rats with moderate renal failure show capillary deficit in heart but not skeletal muscle
K Amann1, K A Neimeier, U Schwarz
1Department of Pathology, University of Heidelberg, Germany.
Insights
Renal failure in rats selectively impairs heart capillarization, leading to reduced capillary density. Skeletal muscle capillarization remained unaffected, indicating tissue-specific abnormalities in cardiac angiogenesis.
Area of Science:
- Cardiovascular Physiology
- Renal Physiology
- Vascular Biology
Background:
- Experimental renal failure is linked to cardiac abnormalities like cardiomyocyte hypertrophy and reduced capillary density.
- These cardiac changes may compromise ischemia tolerance.
- It remains unclear if these structural alterations are heart-specific or occur in other tissues.
Purpose of the Study:
- To investigate whether structural changes, specifically diminished capillarization, observed in the heart during experimental renal failure are unique to cardiac tissue.
- To compare capillarization in the heart versus skeletal muscle in subtotally nephrectomized (SNX) rats.
- To explore potential tissue-specific mechanisms underlying cardiac undercapillarization.
Main Methods:
- Subtotally nephrectomized (SNX) rats and sham-operated pair-fed controls were used.
- Renal failure was maintained for 8 weeks.
- Capillary length density was measured using stereologic techniques in perfusion-fixed skeletal muscle (m. psoas) and hearts.
- Myocyte cross-sectional area and interstitial tissue volume density were also assessed.
Main Results:
- SNX rats exhibited higher systolic blood pressure, serum creatinine, and urea levels, confirming moderate renal failure.
- The heart showed increased myocyte cross-sectional area and interstitial tissue, with significantly reduced myocardial capillary length density in SNX rats.
- Skeletal muscle in SNX rats displayed no significant differences in myocyte cross-sectional area, capillary length density, or capillary-to-fiber ratio compared to controls.
Conclusions:
- Subtotal nephrectomy selectively impairs cardiac capillarization in rats with moderate renal failure.
- The findings suggest a tissue-specific defect in cardiac capillarogenesis, not a generalized vascular abnormality.
- These results highlight unique abnormalities in the heart's microvasculature during renal failure.
Abstract:
In previous studies on experimental renal failure, hypertrophy of cardiomyocytes, diminished capillarization, and increased intercapillary distances had been observed, abnormalities that will expose the heart to reduced ischemia tolerance. It has not been established, however, whether such structural alterations are unique for the heart (eg, as a consequence of left ventricular hypertrophy) or are demonstrable in other tissues as well. Clarification of this point is important to test hypotheses on some potential mechanisms for cardiac undercapillarization. To address this issue further, we compared capillary length density (by stereologic techniques) in perfusion-fixed skeletal muscle (m. psoas) and hearts of subtotally nephrectomized (SNX) rats with moderate renal failure to those in sham-operated pair-fed controls. The duration of renal failure was 8 weeks. SNX rats had significantly higher mean systolic blood pressure (128 mm Hg v 109 mm Hg), serum creatinine, and urea levels. Despite pair feeding, the mean body weight was significantly lower in the SNX rats (409 g v 471 g), but the left ventricular weight to body weight ratio tended to be higher than in the sham-operated controls (2.39 mg/g v 2.13 mg/g). In the heart, myocyte mean cross-sectional area (675 +/- 112 microm2 v 545 +/- 111 microm2) and volume density of nonvascular interstitial tissue (3.47 +/- 1.04 v 1.33 +/- 0.22) were significantly higher in the SNX rats than in the controls. In parallel, myocardial capillary length density was significantly reduced after subtotal nephrectomy (3,036 +/- 535 mm/mm3 v 3,916 +/- 615 mm/mm3). In contrast, in skeletal muscle, myocyte cross-sectional area (3,109 +/- 783 microm2 v 3,042 +/- 639 microm2), capillary length density (718 +/- 248 mm/mm3 v 717 +/- 184 mm/mm3), and three-dimensional capillary fiber ratio (2.10 +/- 0.26 v 2.13 +/- 0.4) were similar in SNX and control rats. These data document a selective defect of capillarization in the heart of animals with moderate renal failure, pointing to tissue-specific abnormalities of cardiac capillarogenesis.