title: Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine.
abstract: In experimental renal failure, increased intramyocardial arteriolar wall thickness, reduced myocardial capillary density, and increased cardiac interstitium are found. The extent to which such alterations can be modified by therapeutic interventions has not been investigated to date. 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 mg/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 techniques. Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three interventions. In contrast, the wall thickness of intramyocardial arterioles was significantly higher in SNX; this was prevented by Ramipril and Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (Lv) was significantly lower and interstitial volume density (Vv) significantly higher in untreated SNX. Reduction of capillary length density was completely prevented by Moxonidine and in part by Ramipril. The increase in cardiac interstitial volume density was completely prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine treatment. The following conclusions can be drawn from the results: (1) all agents normalize aortic wall thickness, but only calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar wall thickening: (2) intramyocardial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the blood pressure to subnormal levels; i.e., changes in systemic blood pressure cannot completely explain the altered vascular structure in renal failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not completely accounted for by their hemodynamic actions.
authors: Department of Internal Medicine, Ruperto Carola University, Heidelberg, Germany.
authors: J
authors: J
authors: Törnig
authors: K
authors: K
authors: Amann
authors: E
authors: E
authors: Ritz
authors: C
authors: C
authors: Nichols
authors: M
authors: M
authors: Zeier
authors: G
authors: G
authors: Mall
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000473:pathology; D001160:Arterioles / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002196:Capillaries / Q000473:pathology; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003331:Coronary Vessels / Q000473:pathology*; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use*; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007093:Imidazoles; D013565:Sympatholytics; D014665:Vasodilator Agents; C043482:moxonidine; D009543:Nifedipine; D017257:Ramipril