<b>Blood pressure, renal biochemical parameters and histopathology in an original rat model of essential hypertension (SHRSP/Kpo </b><b>strain) </b>

Abstract

Hypertensive nephropathy, a consequence of chronic high blood pressure, is increasingly a cause of end-stage renal diseases and its correct management is very important for clinical outcome. Spontaneously hypertensive rat (SHR/Kpo) and stroke-prone SHR (SHRSP/Kpo) strains represent models of human essential hypertension. However, the kidney injuries in SHR/Kpo and SHRSP/ Kpo are not well defined. We therefore characterized the renal pathophysiology of SHR/Kpo and SHRSP/Kpo compared with normotensive control (WKY/Kpo) rats. The SHRSP/Kpo exhibited increased systolic blood pressure at 10 weeks of age, and proteinuria and increased blood urea nitrogen (BUN) and serum creatinine levels at 20 weeks. We simultaneously detected mononuclear cell infiltration, tubular injuries, accumulation of extracellular matrix and marked expression of α-SMA in the tubulointerstitium. Additionally, TGF-β1 and CTGF were up-regulated in the kidney of SHRSP/Kpo. We lastly focused on changes in glomerular cells of SHRSP/Kpo. Nestin, a podocyte marker, was detected but decreased slightly in 20-week-old SHRSP/Kpo. PECAM-1 expression was increased in SHRSP/Kpo glomeruli, indicating the thickening of glomerular endothelial cells. Moreover, we found that α-SMA, a myofibroblast marker, was also upregulated in the glomeruli of SHRSP/Kpo at 20 weeks. These findings suggest that SHRSP/Kpo could be a valuable animal model for human hypertensive nephropathy.

<b>Characteristics of podocyte injury in malignant hypertensive nephropathy of rats (MSHRSP/Kpo </b><b>strain) </b>

“…Stroke-prone spontaneously hypertensive rats (SHRSP/Kpo) represent a useful model of human essential hypertension (12,19). In addition to the tubular lesions, we previously reported the thickened capillary walls in the SHRSP/Kpo glomeruli (12). However, we could not find the distinct injuries in the SHRSP/Kpo podocytes.…”

“…SHR/Kpo and SHRSP/Kpo strains had almost the same level as the WKY/Kpo at 6 weeks of age (12). However, MSHRSP/Kpo exhibited an increase of blood pressure at 6 weeks (Fig.…”

“…We maintained MSHRSP/Kpo and WKY/Kpo (control) rats and measured the blood pressure as described previously (12). All animal experiments were carried out according to the Guideline for Experimental Animal Care issued by the Prime Minister's Office of Japan and approved by the Committee on Animal Experimentation of Kinki University School of Medicine.…”

“…Despite the progress made by many studies in understanding renal damage induced by malignant hypertension, the underlying mechanism of podocyte injury remains unclear. Stroke-prone spontaneously hypertensive rats (SHRSP/Kpo) represent a useful model of human essential hypertension (12,19). In addition to the tubular lesions, we previously reported the thickened capillary walls in the SHRSP/Kpo glomeruli (12).…”

“…The podocytes do not proliferate after birth under normal conditions and are terminally differentiated to maintain an intricate and polarized cellular organization consisting of a cell body, major processes, and foot process sections were used. For synaptopodin, desmin, CD2AP, and nestin staining, 10% formalin-fixed sections were used, as reported previously (11,12). Antigen retrieval was performed by using 1 mM EDTA at pH 8.0 in microwave for 20 min for these staining except PECAM-1 staining.…”