The spontaneously hypertensive rat (SHR) is one of the major models of hypertension. This article describes the current state of knowledge about the mechanism behind kidney damage in SHR in the context of human hypertension and hypertensive kidney disease. It will argue that hypertensive damage in the SHR is pressure-dependent and shows how initial vascular damage leads to a loss of autoregulation and arterial hypertrophy in the juxtamedullary cortex while the outer cortical structures are relatively protected. Progressive arteriolar media hypertrophy then leads to the collapse of some glomeruli followed by tubular atrophy. The reduced glomerular filtration, thus, leads to compensatory hyperfiltration in another population of glomeruli which develop proteinuria and glomerulosclerosis. This model provides some important questions for future research. The regulation of media hypertrophy will be of great interest, as it might slow nephron loss and interstitial fibrosis. Finally, the mechanism by which reduced tubular flow leads to tubular atrophy is another important area for future research. Initial findings indicate that cilia activation may be of major importance for maintaining tubular structure.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
Correspondence to Michael Hultström, Department of Medical Cell Biology, Uppsala University, P.O. Box 571, 75123 Uppsala, Sweden. Tel: +46 18 471 4378; fax: +46 18 471 4938; e-mail: email@example.com
Abbreviations: GFR, glomerular filtration rate; ILA, interlobular artery; RBF, renal blood flow; SHR, spontaneously hypertensive rat; WKY, Wistar–Kyoto rat
Received 13 November, 2011
Revised 6 February, 2012
Accepted 17 February, 2012