Renal lesions and proteinuria in the spontaneously hypertensive rat made normotensive by treatment.
Spontaneously hypertensive rats (SHR) (N = 40) were maintained at normal blood pressure to the age of 100 weeks by treatment (reserpine, hydralazine, and chlorothiazide) beginning at intervals in groups of eight, from the 5th to 45th week. Mortality rates, patterns of proteinuria, and glomerular and arteriolar pathology were compared with that of treated and untreated normotensive Wistar-Kyoto (WKY) controls matched for age (N = 39) and untreated SHR's (N = 26). Treatment clearly prolongs life in SHR's, the mortality rate for untreated being 100% at 75 weeks versus no deaths at that age among 24 SHR's treated before 20th week. At 100 weeks, treated SHR's were excreting eight times the baseline values of urinary protein, whereas WKY's had hardly increased from baseline values. At 100 weeks, normotensive SHR's showed fibrinoid necrosis, sclerosis, and pericapsular fibrosis of glomeruli, whereas no morphologic damage was found in glomeruli or renal arterioles of WKY. Glomerular lesions in normotensive SHR's are indistinguishable in kind from their hypertensive counterparts, but occur somewhat later. Juxtamedullary glomeruli initially suffer the greatest damage and appear to be the major source of urinary protein. These findings speak against the hypothesis of an increased intravascular pressure as the major factor in the pathogenesis of arteriolar sclerosis and rather favor a genetic defect in the vascular system of the SHR, a defect strongly associated with the hypertensive trait. A possible relationship of this defect to inherited membrane abnormalities recently described in RBC and smooth muscle cells of SHR is discussed.
D000367:Age Factors; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D001794:Blood Pressure / Q000187:drug effects; D002740:Chlorothiazide / Q000627:therapeutic use; D006830:Hydralazine / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D007672:Kidney Cortex / Q000098:blood supply / Q000473:pathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology; D007679:Kidney Medulla / Q000098:blood supply / Q000473:pathology*; D008297:Male; D009336:Necrosis / Q000209:etiology; D011507:Proteinuria / Q000209:etiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000627:therapeutic use
D006830:Hydralazine; D002740:Chlorothiazide; D012110:Reserpine