Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

Abstract

Transgenic rats with inducible ANG II-dependent malignant hypertension [TGR(Cyp1a1Ren2)] were generated by inserting the mouse Ren2 renin gene into the genome of the rat. The present study was performed to assess renal morphological changes occurring during the development of ANG II-dependent malignant hypertension in these rats. Male Cyp1a1-Ren2 rats (n = 10) were fed normal rat food containing indole-3-carbinol (I3C; 0.3%) for 10 days to induce malignant hypertension. Rats induced with I3C had higher mean arterial pressures (173 +/- 9 vs. 112 +/- 11 mmHg, P < 0.01) than noninduced normotensive rats (n = 9). Glomerular damage was evaluated by determination of the glomerulosclerosis index (GSI) in tissue sections stained with periodic acid-Schiff. Kidneys of hypertensive rats had a higher GSI than normotensive rats (21.3 +/- 5.6 vs. 3.5 +/- 1.31 units). Quantitative analysis of macrophage ED-1-positive cells and proliferating cell nuclear antigen using immunohistochemistry demonstrated increased macrophage numbers in the renal interstitium (106.4 +/- 11.4 vs. 58.7 +/- 5.0 cells/mm(2)) and increased proliferating cell number in cortical tubules (37.8 +/- 5.7 vs. 24.2 +/- 2.1 cells/mm(2)), renal cortical vessels (2.2 +/- 0.5 vs. 0.13 +/- 0.07 cells/vessel), and the cortical interstitium (33.6 +/- 5.7 vs. 4.2 +/- 1.4 cells/mm(2)) of hypertensive rat kidneys. These findings demonstrate that the renal pathological changes that occur during the development of malignant hypertension in Cyp1a1-Ren2 rats are characterized by inflammation and cellular proliferation in cortical vessels and tubulointerstitium.