Effects of losartan on the blood-brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats.
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.
Kucuk
Mutlu
M
Research Institute for Experimental Medicine, Istanbul University, CAPA-34390 Istanbul, Turkey.
Kaya
Mehmet
M
Kalayci
Rivaze
R
Cimen
Vedat
V
Kudat
Hasan
H
Arican
Nadir
N
Elmas
Imdat
I
Korkut
Ferruh
F
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D005070:Evans Blue; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; D005070:Evans Blue; D019001:Nitric Oxide Synthase; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester