Myocardial interstitial fibrosis in experimental uremia--implications for cardiac compliance.
Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs. 871 +/- 81 in controls, P less than 0.05) with an increase of both right and left ventricular weight. This was accompanied by reduction of capillary cross-sectional area despite unchanged capillary length. The volume density (cm3/cm3) of cardiomyocytes was unchanged (0.881 +/- 0.01 vs. 0.871 +/- 0.016 in controls), but volume density of interstitial tissue (excluding capillary lumen) was significantly increased (0.042 +/- 0.011 cm3 interstitial tissue/cm3 total heart tissue vs. 0.019 +/- 0.007 in controls). This was associated with signs of activation of interstitial cells, that is, increased volume of interstitial cell nuclei and interstitial cell cytoplasm. Concomitantly, a significant increase of volume density of non-cellular interstitial ground substance was found which was not normalized by antihypertensive treatment using Ramipril. After three months of uremia, electron microscopy showed collagen fiber deposition in the interstitium. Comparable interstitial fibrosis was not observed in hearts of rats with renovascular (one clip-two kidney) hypertension. It is concluded that uremia increases myocardial interstitial ground substance by mechanisms independent of hypertension. The data may be relevant for recent findings of diastolic heart malfunction secondary to impaired compliance in uremic patients.
Mall
G
G
Department Pathology, University of Heidelberg, Republic of Germany.
Rambausek
M
M
Neumeister
A
A
Kollmar
S
S
Vetterlein
F
F
Ritz
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D009392:Nephrectomy; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000150:complications* / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D017257:Ramipril