Unit

UNIT 5.53 Models of Cardiovascular Disease: Measurement of Antihypertensive Activity in the Conscious Rat (SHR, DOCA-Salt, and Goldblatt Hypertension Models)

  1. Philippe Guillaume1,
  2. Daniel Provost1,
  3. Pamela Legrand1,
  4. Michael Godes2,
  5. Pierre Lacroix1

Published Online: 1 MAR 2009

DOI: 10.1002/0471141755.ph0553s44

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Guillaume, P., Provost, D., Legrand, P., Godes, M. and Lacroix, P. 2009. Models of Cardiovascular Disease: Measurement of Antihypertensive Activity in the Conscious Rat (SHR, DOCA-Salt, and Goldblatt Hypertension Models). Current Protocols in Pharmacology. 44:5.53:5.53.1–5.53.15.

Author Information

  1. 1

    Porsolt and Partners Pharmacology, Boulogne-Billancourt, France

  2. 2

    Center for Cardiovascular Research/Institute of Pharmacology, Berlin, Germany

Publication History

  1. Published Online: 1 MAR 2009
  2. Published Print: MAR 2009

Abstract

The protocols described in this unit are used to assess the effects of new chemical entities on hypertension in conscious rats. In the spontaneously hypertensive rat (SHR) model, the results obtained with the reference compounds clonidine, prazosin, propranolol, and captopril are provided for illustration. All compounds demonstrate antihypertensive activity, with captopril and prazosin being the least and the most active, respectively. In the deoxycorticosterone acetate (DOCA)-salt model in the rat, the test substance shown as an example (a potential endothelin ETA-receptor antagonist) prevents the development of hypertension in the first phase. However, the effects of treatment disappear in the very last phase of the study, suggesting the development of a malignant hypertension resistant to treatment in this model. In the Goldblatt hypertension rat model (renal artery stenosis), losartan prevents the development of hypertension. It does not modify the weight of the right and left kidneys but slightly reduces the degree of cardiac hypertrophy. Curr. Protoc. Pharmacol. 44:5.53.1-5.53.15. © 2009 by John Wiley & Sons, Inc.

Keywords:

  • cardiovascular disease;
  • hypertension;
  • SHR;
  • DOCA-salt;
  • Goldblatt hypertension