Functional and structural correlates of glomerulosclerosis after renal mass reduction in the rat.
Previously, it was shown that 5/6 renal mass reduction by surgical excision (RK-NX) results in a marked reduction of glomerulosclerosis (GS) at 6 wk compared with the conventional 5/6 renal ablation by infarction (RK-I) model. To determine the pathogenetic correlates of the striking differences in GS, radiotelemetrically measured BP; single nephron function; glomerular volume; the temporal expression of mRNA for renin, transforming growth factor-beta, and platelet-derived growth factor-B; and plasma renin concentration were compared between RK-NX, RK-I, and sham-operated control rats. Hypertension only developed in the RK-I model, was present at 3 d after infarction, and was correlated with both an increased expression of renin mRNA by Northern analysis and elevated plasma renin concentration. Structural (glomerular volume) and functional (single nephron blood flow and GFR) indices of the compensatory adaptive response were significantly but similarly increased in the RK-NX and RK-I rats compared with sham-operated controls, indicating that these adaptations per se are not responsible for the initiation of GS after 5/6 renal mass reduction. Glomerular capillary pressure (P(GC)) was also significantly increased in both RK-I (56 +/- 2 mmHg) and RK-NX rats (50 +/- 0.9 mmHg) compared with controls (46 +/- 0.8 mmHg, P < 0.01), but the increase was significantly greater in RK-I versus RK-NX rats (P < 0.05) consistent with the higher BP in RK-I rats. These data indicate that differences in renin probably account for the early divergence of BP (and P(GC)) responses between RK-I and RK-NX models. Transforming growth factor-beta and platelet-derived growth factor-B mRNA expression in pooled RNA from kidneys from each group showed increases at 21 d along with early evidence of glomerular injury in the RK-I group but not in the RK-NX group, consistent with their postulated roles as molecular mediators of GS, but only in rats with pathologic glomerular hypertension.
Griffin
Karen A
KA
Department of Medicine, Loyola University Medical Center/Hines VA Hospital, Maywood, Illinois.
Picken
Maria M
MM
Department of Pathology, Loyola University Medical Center/Hines VA Hospital, Maywood, Illinois.
Churchill
Monique
M
Department of Physiology, Wayne State University, Detroit, Michigan.
Churchill
Paul
P
Department of Physiology, Wayne State University, Detroit, Michigan.
Bidani
Anil K
AK
Department of Medicine, Loyola University Medical Center/Hines VA Hospital, Maywood, Illinois.
D000818:Animals; D001794:Blood Pressure; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy / Q000379:methods; D009399:Nephrons / Q000473:pathology / Q000503:physiopathology; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics
D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D012083:Renin