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

Kucuk M., Kaya M., Kalayci R., Cimen V., Kudat H., Arican N., ...More

LIFE SCIENCES, vol.71, no.8, pp.937-946, 2002 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 71 Issue: 8
  • Publication Date: 2002
  • Doi Number: 10.1016/s0024-3205(02)01772-1
  • Journal Name: LIFE SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.937-946
  • Keywords: L-NAME, Angiotensin II, hypertension, Evans blue, blood-brain barrier, SUPEROXIDE ANION, INHIBITION, DISRUPTION, MECHANISMS, EDEMA, FLOW
  • Istanbul University Affiliated: Yes


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 mug/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. (C) 2002 Elsevier Science Inc. All rights reserved.