Control of blood pressure and end-organ damage in maturing salt-loaded stroke-prone spontaneously hypertensive rats by oral angiotensin II receptor blockade

Camargo, M. J. F.; Lutterotti, Nicola von; Campbell, Wallace G.; Pecker, Mark S.; James, Gary D.; Timmermans, Pieter B.M.W.M.; Laragh, John H.

doi:10.1097/00004872-199301000-00006

Cited by 63 publications

(29 citation statements)

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“…In stroke-prone hypertensive rats, di- minishing RAS activity with potassium, 24 captopril, 25 or losartan 26,27 prevented stroke occurrence without lowering blood pressure. Moreover, studies in a model of acute stroke induced by carotid ligation in gerbils suggest that AT 2 receptor stimulation may mediate cerebrovascular anti-ischemic effects.…”

Section: Discussionmentioning

confidence: 99%

Stroke Reduction in Hypertensive Adults With Cardiac Hypertrophy Randomized to Losartan Versus Atenolol

et al. 2005

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Abstract-The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study showed that treatment with the angiotensin II type-1 receptor antagonist losartan reduces overall stroke risk compared with conventional therapy with the ␤-blocker atenolol. We conducted secondary analyses in LIFE to determine the extent to which the cerebrovascular benefits of losartan apply to different clinical subgroups and stroke subtypes and to assess the dependence of these benefits on baseline and time-varying covariates. Although comparable risk reductions occurred for hemorrhagic and embolic stroke, these were not statistically significant. The number of neurological deficits per stroke was similar, but there were fewer strokes in the losartan group for nearly every level of stroke severity. Effects were consistent in all clinical subgroups except for those defined by age and ethnicity. The benefits of losartan on all strokes were independent of baseline and time-varying risk factors, including blood pressure. The number needed to treat for 5 years to prevent 1 stroke was 54 for the average participant, declining to 25, 24, and 9 for patients with cerebrovascular disease, isolated systolic hypertension, and atrial fibrillation, respectively. In conclusion, substantial cerebrovascular benefit could be realized with the institution of losartan-based therapy over conventional therapy among hypertensive patients with left ventricular hypertrophy across the spectrum of cardiovascular risk.

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Section: Discussionmentioning

confidence: 99%

Stroke Reduction in Hypertensive Adults With Cardiac Hypertrophy Randomized to Losartan Versus Atenolol

et al. 2005

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“…[11][12][13][14][15] When losartan at the doses of 1 and 10 mg/kg/day, which afforded none and only moderate anti-hypertensive effects, respectively, was administered to salt-loaded 5-week-old SHRSP for 15 weeks, losartan (1 and 10 mg/kg) completely suppressed stroke and mortality and strongly opposed (1 mg/kg) and abolished (10 mg/kg) the increase in proteinuria observed in the control. 11 Losartan markedly limited (1 mg/kg) or abolished (10 mg/kg) vascular fibrinoid necrosis formation in the brain, kidney and heart.…”

Section: Discussionmentioning

confidence: 99%

“…Losartan increased survival and completely prevented cerebrovascular infarcts. 13 Losartan was also effective in the prevention of stroke at a dose which had no effect on BP. 14 Candesartan (CV-11974) lowered BP in a manner similar to hydralazine, but reduced urinary protein excretion more than hydralazine in SHRSP.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Nishikawa

1998

J Hum Hypertens

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This review describes how angiotensin AT 1 receptor antagonists (eg, candesartan cilexetil, losartan) effectively protect against end-organ damage including stroke, cardiac hypertrophy, renal dysfunction, glomerulosclerosis, and/or vascular hypertrophy in the models of stroke-prone spontaneously hypertensive rats (SHRSP), SHR, DOCA/salt hypertensive rats, Dahl hypertensive rats and/or 5/6 nephrectomised rats. Particularly in SHRSP and DOCA/salt hypertensive rats, candesartan cilexetil markedly reduced the incidence of stroke and renal injury even at doses which had no effect on blood pressure (BP), suggesting that the tissue protective effects of angiotensin AT 1 antagonists are not attributable simply to the normalisation of BP. In the heart, kidney and vascular tissues of SHRSP and the kidney of DOCA/salt hypertensive rats, the mRNA

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“…9,11,12 They were given vehicle (nϭ25) or pioglitazone (1 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ) (nϭ23) by gastric gavage once a day for 1 month (31 days). Blood pressure was measured by the tail-cuff method.…”

Section: Effect Of Pioglitazone On Stroke and Survival Rate In Shrspmentioning

confidence: 99%

Pioglitazone Exerts Protective Effects Against Stroke in Stroke-Prone Spontaneously Hypertensive Rats, Independently of Blood Pressure

Nakamura

Yamamoto

Kataoka

et al. 2007

Stroke

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Background and Purpose-Very recent subgroup analysis from the PROspective pioglitAzone Clinical Trial In macroVascular Events has shown that pioglitazone reduces the risk of recurrent stroke in type 2 diabetic patients. However, the underlying mechanism of stroke prevention by pioglitazone is unknown. Our aim was to examine the effect of pioglitazone on hypertension-based stroke in rats.was orally administered to stroke-prone spontaneously hypertensive rats (SHRSP) to examine the effect on incidental stroke, cerebrovascular injury, brain inflammation, oxidative stress, and vascular endothelial dysfunction induced by hypertension. Results-Treatment of SHRSP with pioglitazone for 4 weeks, without affecting blood pressure and blood glucose values, improved vascular endothelial dysfunction (PϽ0.05), suppressed remodeling of the middle cerebral artery (PϽ0.05) and brain microvessels (PϽ0.05), and inhibited brain macrophage infiltration (PϽ0.05) and the upregulation of brain monocyte chemoattractant protein-1 and tumor necrosis factor-␣ expression (PϽ0.01). Furthermore, pioglitazone treatment significantly delayed the onset of stroke signs and death in SHRSP (PϽ0.05). These beneficial effects of pioglitazone on cerebrovascular injury and stroke in SHRSP were associated with a reduction of brain and vascular superoxide via the inhibition of NADPH oxidase activity. Conclusions-Our work provides the first evidence that pioglitazone significantly protects against hypertension-induced cerebrovascular injury and stroke by improving vascular endothelial dysfunction, inhibiting brain inflammation, and reducing oxidative stress. These beneficial effects of pioglitazone were independent of blood pressure or blood sugar values. Thus, pioglitazone appears to be a potential therapeutic agent for stroke in type 2 diabetes with hypertension.

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Control of blood pressure and end-organ damage in maturing salt-loaded stroke-prone spontaneously hypertensive rats by oral angiotensin II receptor blockade

Cited by 63 publications

References 0 publications

Stroke Reduction in Hypertensive Adults With Cardiac Hypertrophy Randomized to Losartan Versus Atenolol

Stroke Reduction in Hypertensive Adults With Cardiac Hypertrophy Randomized to Losartan Versus Atenolol

Angiotensin AT1 receptor antagonism and protection against cardiovascular end-organ damage

Pioglitazone Exerts Protective Effects Against Stroke in Stroke-Prone Spontaneously Hypertensive Rats, Independently of Blood Pressure

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