The renin-angiotensin system in the brain: possible therapeutic implications for AT1-receptor blockers

Čulman, Juraj; Blume, Annegret; Gohlke, Peter; Unger, Thomas

doi:10.1038/sj.jhh.1001442

Cited by 98 publications

(96 citation statements)

References 38 publications

(42 reference statements)

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“…There is a possible mechanism that orally treated olmesartan acted on the AT1 receptors of the circumventricular organ and area postrema that lacks blood-brain barrier, thereby inhibiting AT1 receptors within the brain through neural pathway. 5,44 This indirect action of olmesartan could also attenuate oxidative stress in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports, however, showed that AT1-receptor blockers act within the brain, as well as in the peripheral vasculature. [5][6][7][8][9][10]43,44 Different AT1 blockers may thus act centrally or peripherally and block different AT1 receptors. 8,44 Lipophilicity and pharmacokinetics are important factors for determining blood-brain barrier permeability.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7][8][9][10]43,44 Different AT1 blockers may thus act centrally or peripherally and block different AT1 receptors. 8,44 Lipophilicity and pharmacokinetics are important factors for determining blood-brain barrier permeability. [8][9][10] Although olmesartan has a lipophilic property, its active form RNH-6270 has a hydrophilic property and a strong AT1 receptor binding capacity.…”

Section: Discussionmentioning

confidence: 99%

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Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method

et al. 2009

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We previously showed that oxidative stress in the brain is involved in the neural mechanisms of hypertension. Therefore, olmesartan, an angiotensin type 1 receptor blocker, might affect oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). Here, we evaluated the effects of olmesartan treatment using an in vivo electron spin resonance (ESR)/spin probe technique. Two groups of SHRSP were treated with either olmesartan (10 mg kg À1 day À1 ) or hydralazine (Hyd, 20 mg kg À1 day À1 )/hydrochlorothiazide (HCT, 4.5 mg À1 kg day À1 ) for 30 days (n¼5 for each). Systolic blood pressure decreased similarly in both groups after treatment. Heart rate and urinary norepinephrine (NE) excretion increased in rats treated with Hyd/HCT, but not in those treated with olmesartan. The in vivo ESR signal decay rates of the blood-brain barrierpermeable spin probe methoxycarbonyl-PROXYL were significantly higher in SHRSP brains than in age-matched normotensive Wistar-Kyoto rat brains (Po0.01; n¼6 for each). Olmesartan attenuated the ESR signal decay rates in SHRSP brains, but Hyd/HCT did not. Intracerebroventricular infusion of active form of olmesartan, RNH-6270, reduced blood pressure and NE excretion, and the ESR signal decay rate was reduced in SHRSP brains. These findings indicate that olmesartan has anti-oxidative property in the brain without stimulating reflex-mediated sympathetic activity in SHRSP.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method

et al. 2009

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“…[4][5][6][7][8] Growing evidence has suggested that the reninangiotensin system (RAS) in the central nervous system participates in the processing of sensory information, learning and memory. 9,10 Brain angiotensin II (Ang II) and its fragments Ang IV and Ang III have been shown to influence performance in learning and memory paradigms directly or by modulating the activity of other neurotransmitters, like acetylcholine, catecholamines, serotonin and other peptides. [11][12][13] Beyond being implicated in neuronal functions regulation, these neurotransmitters also regulate local vasomotility and endothelium-dependent relaxation, which is of relevance for maintaining the physiological self-regulation of brain flow, that is presumed to be necessary to correct performance of cerebral functions.…”

Section: Introductionmentioning

confidence: 99%

Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients

et al. 2005

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The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/ HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61-75 years, with sitting diastolic blood pressure (DBP) 490 mmHg and o110 mmHg and systolic blood pressure (SBP) 4140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallelgroup design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, wordlist recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/ HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score ( þ 17.1 and þ 15.7%, respectively, Po0.05 vs baseline), the word-list recall score ( þ 13.5 and þ 16.9%, Po0.05) and the Trails B score (À33 and À30.5%, Po0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.

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“…the At1 receptor antagonist telmisartan can penetrate the blood-brain barrier in a dose and time-dependent manner to inhibit centrally mediated effects of angiotensin II [12]. telmisartan is more liphophilic and has greater potency at brain At1 receptors [13]. Angiotensin II receptor subtypes, called At1 and At2 are engaged in action of angiotensin II.…”

Section: Ptz Induced Seizuresmentioning

confidence: 99%

Evaluation and Comparison of Anticonvulsant Activity of t elmisartan and Olmesartan in Experimentally Induced Animal Models of Epilepsy

Pushpa

Suresha

et al. 2014

JCDR

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The renin-angiotensin system in the brain: possible therapeutic implications for AT1-receptor blockers

Cited by 98 publications

References 38 publications

Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method

Olmesartan reduces oxidative stress in the brain of stroke-prone spontaneously hypertensive rats assessed by an in vivo ESR method

Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients

Evaluation and Comparison of Anticonvulsant Activity of t elmisartan and Olmesartan in Experimentally Induced Animal Models of Epilepsy

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