ARTERIOLAR WALL THICKENING, CAPILLARY RAREFACTION AND INTERSTITIAL FIBROSIS IN THE HEART OF RATS WITH RENAL-FAILURE - THE EFFECTS OF RAMIPRIL, NIFEDIPINE AND MOXONIDINE

In experimental renal failure, increased intramyocardial arteriolar wa ll thickness, reduced myocardial capillary density, and increased card iac interstitium are found. The extent to which such alterations can b e modified by therapeutic interventions has not been investigated to d ate. The purpose of this study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 m g/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk, After perfusion fixation, heart and aorta were examined by stereological tec hniques, Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three int erventions. In contrast, the wall thickness of intramyocardial arterio les was significantly higher in SNX; this was prevented by Ramipril an d Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (L(v)) was significantly lower and interstitial volume density (V-v) significantly higher in untreated SNX. Reduction of capillary l ength density was completely prevented by Moxonidine and in part by Ra mipril. The increase in cardiac interstitial volume density was comple tely prevented by Ramipril and was partially prevented by Moxonidine o r Nifedipine treatment, The following conclusions can be drawn from th e results: (1) all agents normalize aortic wall thickness, but only ca lcium channel blockers and angiotensin-converting enzyme (ACE) inhibit ors prevent intramyocardial arteriolar wall thickening; (2) intramyoca rdial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the b lood pressure to subnormal levels; i.e., changes in systemic blood pre ssure cannot completely explain the altered vascular structure in rena l failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not comple tely accounted for by their hemodynamic actions.