Renal thrombotic microangiopathy in a genetic model of hypertension in mice

Sanjeev Sethi, Shinichiro Iida, Curt D. Sigmund, Donald D. Heistad

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Our goal was to develop a model of accelerated hypertension with renal microangiopathy. Transgenic mice that are hypertensive because of overexpression of human renin (R+ mice) and human angiotensin (A+ mice) genes were studied. To increase arterial pressure to levels comparable to those that may be seen in malignant hypertension, high salt was added to the diet and/or the nitric oxide synthase inhibitor, Nω-nitro-L-arginine methylester (L-NAME), was added to the drinking water. Renal lesions, decline in renal function, and proteinuria developed within 10 weeks in R +/A+ mice given both L-NAME and a high-salt diet, and within 24 weeks in mice given either L-NAME or a high-salt diet. Renal morphology showed features of severe thrombotic microangiopathy, with extensive vascular and glomerular lesions in all R+/A+ mice on high salt, L-NAME, or high salt plus L-NAME. Vascular lesions included fibrin thrombi and onion skinning of the vessel walls, whereas glomerular lesions included segmental sclerosis, mesangiolysis, fibrin thrombi within glomerular capillaries, and double-contour formation of glomerular capillary walls. Renal morphology was normal in control mice fed high salt and/or L-NAME. No R +/A+ mice fed a normal diet developed vascular lesions, whereas a few mice developed mild focal glomerular lesions. In summary, these studies characterize vascular and glomerular lesions in R+/A + mice fed high salt, L-NAME, or both high salt and L-NAME, and provide a murine model of malignant hypertension with renal thrombotic microangiopathy.

Original languageEnglish (US)
Pages (from-to)196-203
Number of pages8
JournalExperimental Biology and Medicine
Volume231
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Hypertension
  • Renal thrombotic microangiopathy
  • Renin angiotensin
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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