Effects of losartan on the blood-brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats

Life Sci. 2002 Jul 12;71(8):937-46. doi: 10.1016/s0024-3205(02)01772-1.


Hypertension is closely associated with vascular endothelial dysfunction. The aim of this study was to investigate the effects of Angiotensin II (ANG II) receptor antagonist losartan on the blood-brain barrier (BBB) permeability in L-NAME-induced hypertension and/or in ANG II-induced acute hypertension in normotensive and hypertensive rats. Systolic blood pressure was measured by tail cuff method before, during and following L-NAME treatment (1 g/L). Losartan (3 mg/kg) was given to the animal for five days. Acute hypertension was induced by ANG II (60 microg/kg). Arterial blood pressure was directly measured on the day of the experiment. BBB disruption was quantified according to the extravasation of the albumin-bound Evans blue dye. Losartan significantly reduced the mean arterial blood pressure from 169 +/- 3.9 mmHg to 82 +/- 2.9 mmHg in L-NAME and from 171 +/- 2.9 mmHg to 84 +/- 2.9 in L-NAME plus losartan plus ANG II groups (p < 0.05). The content of Evans blue dye in the cerebral cortex significantly increased in L-NAME (p < 0.01). Moreover, the content of Evans blue dye markedly increased in the cerebellum (p < 0.001) and slightly increased in diencephalon region (p < 0.05) in L-NAME plus ANG II. Losartan reduced the increased BBB permeability to Evans blue dye in L-NAME (p < 0.01) and L-NAME plus ANG II (p < 0.001). These results indicate that L-NAME and L-NAME plus ANG II both lead to an increase in microvascular Evans blue dye efflux to brain, and losartan treatment attenuates this protein-bound dye transport into brain tissue presumably due to its protective effect on endothelial cells of brain vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology
  • Angiotensin Receptor Antagonists*
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects
  • Blood-Brain Barrier / drug effects*
  • Coloring Agents
  • Enzyme Inhibitors
  • Evans Blue
  • Hypertension / chemically induced
  • Hypertension / physiopathology*
  • Losartan / pharmacology*
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats
  • Rats, Wistar


  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Coloring Agents
  • Enzyme Inhibitors
  • Angiotensin II
  • Nitric Oxide
  • Evans Blue
  • Nitric Oxide Synthase
  • Losartan
  • NG-Nitroarginine Methyl Ester