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

Küçük, Mutlu; Kaya, Mehmet; Kalayci, Rivaze; Cimen, Vedat; Kudat, Hasan; Arıcan, Nadir; Elmas, İmdat; Korkut, Ferruh

doi:10.1016/s0024-3205(02)01772-1

Cited by 39 publications

(24 citation statements)

References 26 publications

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“…One could speculate that AGT metabolites are critical for BBB and peripheral vascular formation during the prenatal period, a phenomenon that closely resembles vascular repair. Many studies have described a detrimental role of the RAS with regards to brain edema in experimental animal models of stroke (Blezer et al, 2001;Ito et al, 2001;Kucuk et al, 2002;Lou et al, 2004), observations seemingly divergent from ours. Such differences can be explained by the fact that most studies were conducted in hypertensive animals, a model in which subclinical BBB dysfunction is certainly present, and during which CNS compensatory mechanisms probably occur.…”

Section: Discussioncontrasting

confidence: 91%

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Cayrol²,

et al. 2007

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The blood-brain barrier (BBB) restricts molecular and cellular trafficking between the blood and the CNS. Although astrocytes are known to control BBB permeability, the molecular determinants of this effect remain unknown. We show that angiotensinogen (AGT) produced and secreted by astrocytes is cleaved into angiotensin II (AngII) and acts on type 1 angiotensin receptors (AT 1 ) expressed by BBB endothelial cells (ECs). Activation of AT 1 restricts the passage of molecular tracers across human BBB-derived ECs through threonine-phosphorylation of the tight junction protein occludin and its mobilization to lipid raft membrane microdomains. We also show that AGT knock-out animals have disorganized occludin strands at the level of the BBB and a diffuse accumulation of the endogenous serum protein plasminogen in the CNS, compared with wild-type animals. Finally, we demonstrate a reduction in the number of AGT-immunopositive perivascular astrocytes in multiple sclerosis (MS) lesions, which correlates with a reduced expression of occludin similarly seen in the CNS of AGT knock-out animals. Such a reduction in astrocyte-expressed AGT and AngII is dependent, in vitro, on the proinflammatory cytokines tumor necrosis factor-␣ and interferon-␥. Our study defines a novel physiological role for AngII in the CNS and suggests that inflammation-induced downregulation of AngII production by astrocytes is involved in BBB dysfunction in MS lesions.

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Section: Discussioncontrasting

confidence: 91%

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Cayrol²,

et al. 2007

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“…The findings are also in good consent with the literature data documenting beneficial effect of AT1R blockade on BP (Kawano et al 1994), antiproliferative impact on smooth muscle cells of conduit arteries (Koprdova et al, 2009), inflammation (Ando et al 2004b;Benicky et al 2009), and NOS expression in cerebral vessels and microvessels of SHR (Yamakawa et al 2003). In the experimental model of hypertension induced by long-term administration of L-NAME, losartan reduced the increased permeability of the blood-brain barrier (Kucuk et al 2002).…”

Section: Discussionsupporting

confidence: 87%

“…Additionally, the remodeling of the middle cerebral artery and significantly altered expression of endothelial and inducible forms of NOS in the artery and brain microvessels in SHR were demonstrated (Yamakawa et al 2003). The increased permeability of blood-brain barrier (Johansson 1999;Kucuk et al 2002) and inflammation in cerebral vasculature and brain tissue also occur in hypertension (Ando et al 2004b;Sun et al 2006).…”

Section: Introductionmentioning

confidence: 98%

Losartan improved respiratory function and coenzyme Q content in brain mitochondria of young spontaneously hypertensive rats

2010

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Increased production of free radicals and impairment of mitochondrial function are important factors in the pathogenesis of hypertension. This study examined the impact of hypertension on mitochondrial respiratory chain function, coenzyme Q(9) (CoQ(9)), coenzyme Q(10) (CoQ(10)), and alpha-tocopherol content in brain mitochondria, and the effect of blockade of angiotensin II type 1 receptors (AT1R) in the prehypertensive period on these parameters. In addition, blood pressure, heart and brain weight to body weight ratios, and the geometry of the basilar artery supplying the brain were evaluated. In the 9th week blood pressure and heart weight/body weight ratio were significantly increased and brain weight/body weight ratio was significantly decreased in spontaneously hypertensive rats (SHR) when compared to Wistar rats (WR). The cross-sectional area of the basilar artery was increased in SHR. Glutamate-supported respiration, the rate of ATP production, and concentrations of CoQ(9), CoQ(10), and alpha-tocopherol were decreased in SHR. The succinate-supported function and cytochrome oxidase activity were not changed. The treatment of SHR with losartan (20 mg/kg/day) from 4th to 9th week of age exerted preventive effect against hypertension, heart and arterial wall hypertrophy, and brain weight/body weight decline. After the therapy, the rate of ATP production and the concentration of CoQ increased in comparison to untreated SHR. The impairment of energy production and decreased level of lipid-soluble antioxidants in brain mitochondria as well as structural alterations in the basilar artery may contribute to increased vulnerability of brain tissue in hypertension. Long-term treatment with AT1R blockers may prevent brain dysfunction in hypertension.

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“…Essential hypertension has been associated with defects in the production or action of NO, chronic deficiency of which is a well established hypertensive model (Baylis et al, 1992;Moncada and Higgs, 1993;Blot et al, 1994;Kucuk et al, 2002;Suda et al, 2002;Zhao et al, 2002;Ahishali et al, 2005). This model has been used in the evaluation of experimental vascular lesions in heart and kidney as well as central nervous system (Baylis et al, 1992;Blot et al, 1994;Suda et al, 2002;Zhao et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Defects in the synthesis and/or release of NO might play an important role in the endothelial dysfunction of normal or hypertensive vessels. Recent studies with contradictory results have indicated that the activation (Shyamaladevi et al, 2002) or the inhibition (Prado et al, 1992;Jansson et al, 1999;Kucuk et al, 2002) of NO synthase provoked the macromolecules' leakage to the brain. Life Sciences 79 (2006) 16 -20 www.elsevier.com/locate/lifescie NO is regarded as an important pathogenic component in seizure induction.…”

Section: Introductionmentioning

confidence: 99%

Long-term l-NAME treatment potentiates the blood–brain barrier disruption during pentylenetetrazole-induced seizures in rats

et al. 2006

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

Cited by 39 publications

References 26 publications

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Angiotensin II Controls Occludin Function and Is Required for Blood–Brain Barrier Maintenance: Relevance to Multiple Sclerosis

Losartan improved respiratory function and coenzyme Q content in brain mitochondria of young spontaneously hypertensive rats

Long-term l-NAME treatment potentiates the blood–brain barrier disruption during pentylenetetrazole-induced seizures in rats

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