Renal lesions and proteinuria in the spontaneously hypertensive rat made normotensive by treatment.

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. Juxta-medullary 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. Lesions renales et proteinurie chez le rat spontanement hypertendu rendu normotendu par le traitement. Des rats spontanement hypertendu (SH) (N = 40) ont ete maintenus a une pression arterielle normale jusqu'a l'âge de 100 semaines par un traitement (reserpine, hydralazine et chlorothiazide) commencant a des temps differents pour chaque groupe de huit rats entre la 5e et la 45e semaine. La mortalite, les modalites de la proteinurie et de la pathologie glomerulaire et arteriolaire ont ete comparees a celles de rats controles Wistar-Kyoto (WKY), apparies pour l'age, traites ou non traites (N = 39) et de rats SHR non traites (N = 26). Le traitement prolonge la duree de vie de SHR de facon importante, la mortalite en l'absence de traitement etant 100% a 75 semaines par opposition a l'absence de morts au meme age parmi 24 SHR traites avant la 20e semaine. A 100 semaines les SHR traites avaient une excretion urinaire de proteines egale a 8 fois la valeur basale alors que les WKY n'avaient pratiquement pas augmente leur excretion par rapport a la valeur basale. A 100 semaines les SHR normotendus avaient de la necrose fibrinoide, de la sclerose et de la fibrose pericapsulaire des glomerules alors qu'il n'a pas ete observe d'anomalies morphologiques des glomerules ou des arterioles renales chez les WKY. Les lesions glomerulaires des SHR normotendus ne sont pas differentes de celles de leurs homologues hypertendus mais elles surviennent un peu plus tard. Les glomerules juxtamedullaires subissent en premier les lesions les plus importantes et semblent etre la source majeure de la proteinurie Ces constatations vont a rencontre de l'hypothese d'une augmentation de la pression intravasculaire comme facteur majeur de la sclerose arteriolaire et sont plutot en faveur d'un deficit genetique du systeme vasculaire des SHR, deficit fortement associe au trait hypertensif. Une relation possible de ce deficit avec les anomalies membranaires hereditaires recemment decrites dans le globule rouge et les cellules musculaires lisses de SHR est discutee.