title: Effects of losartan on the blood-brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats.
abstract: 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.
authors.affiliation: Research Institute for Experimental Medicine, Istanbul University, CAPA-34390 Istanbul, Turkey.
authors.forename: Mutlu
authors.initials: M
authors.lastname: Kucuk
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kaya
authors.forename: Rivaze
authors.initials: R
authors.lastname: Kalayci
authors.forename: Vedat
authors.initials: V
authors.lastname: Cimen
authors.forename: Hasan
authors.initials: H
authors.lastname: Kudat
authors.forename: Nadir
authors.initials: N
authors.lastname: Arican
authors.forename: Imdat
authors.initials: I
authors.lastname: Elmas
authors.forename: Ferruh
authors.initials: F
authors.lastname: Korkut
mesh_terms: 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
chemical_list: 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