Evolution of renal interstitial inflammation and NF-kappaB activation in spontaneously hypertensive rats.
Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive rats (SHR) and interventions leading to their reduction are associated with improvement of the hypertension. The present studies examined the evolution of the interstitial inflammation in the natural course of the SHR to gain insight on the potential role of interstitial immune cell accumulation in the development of hypertension. We studied SHR and control WKY rats at 3 weeks (SHR-3 wk group, n = 11 and WKY-3 wk group, n = 10), 11 weeks (SHR-11 wk group, n = 5 and WKY-11 wk group, n = 5) and 24 weeks (SHR-24 wk group, n = 10 and WKY-24 wk group, n = 10). The SHR-3 wk group was normotensive and older SHR developed hypertension that was severe in the SHR-24 wk group. Tubulointerstitial accumulation of lymphocytes, macrophages, angiotensin II-positive cells, cells expressing the p65 DNA-binding subunit of NF-kappaB and activation of NF-kappaB in the kidney were all significantly increased (p < 0.01) in the prehypertensive SHR-3 wk group and augmented progressively, with the highest values in the SHR-24 wk group. The SHR-24 wk group showed increased (p < 0.001) helper (CD4) T cell infiltration and a high CD4/CD8 ratio. These findings are consistent with the possibility that activation of NF-kappaB and renal interstitial infiltration of immune cells may be part of the pathophysiologic process that drives hypertension in the SHR.
Rodríguez-Iturbe
Bernardo
B
Renal Service, Hospital Universitario de Maracaibo, Instituto de Investigaciones Biomédicas, Fundacite-Zulia, Universidad del Zulia, Maracaibo, Venezuela. bernardori@telcel.net.ve
Quiroz
Yasmir
Y
Ferrebuz
Atilio
A
Parra
Gustavo
G
Vaziri
Nosratola D
ND
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001706:Biopsy; D001794:Blood Pressure; D016516:CD4-CD8 Ratio; D003404:Creatinine / Q000097:blood; D006977:Hypertension, Renal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016328:NF-kappa B; D000804:Angiotensin II; D003404:Creatinine