Simvastatin Reduces Pressor Response to Centrally Administered Angiotensin II

Ufnal, Marcin; Sikora, Mariusz; Żera, Tymoteusz; Szczepañska‐Sadowska, Ewa

doi:10.1038/ajh.2010.103

Cited by 10 publications

(13 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study we found that simvastatin treatment reduces pressor responses to centrally infused AngII, which is in line with previous observations . However, in contrast with our previous study, the antihypertensive effect of simvastatin was associated with a reduction in blood cholesterol. This discrepancy most likely results from differences in simvastatin treatment regimens between the two studies.…”

Section: Discussionsupporting

confidence: 92%

“…To exclude peripheral actions of the compounds under investigation, we used the lowest doses of AngII (10 ng) and VP (20 ng) that were sufficient to cause significant hypertensive responses when given i.c.v. but did not affect mean arterial blood pressure (MABP) or heart rate (HR) when infused intravenously . Similarly, we infused 10 μg losartan and 400 ng d(CH 2 ) 5 [Tyr(Me) 2 ,Ala‐NH 2 9 ]VP because these doses have been found to abolish pressor responses to centrally, but not peripherally, administered AngII and VP, respectively …”

Section: Methodsmentioning

confidence: 99%

“…Previously, we found that simvastatin given in drinking water (20 mg/L) for 12 weeks reduces the pressor response to intracerebroventricular (i.c.v.) infusions of AngII in normotensive rats …”

Section: Introductionmentioning

confidence: 99%

“…infusions of AngII, VP and their antagonists. In addition, we determined whether our previous findings of an interaction between simvastatin and AngII could be replicated using a different simvastatin treatment regimen.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Oral simvastatin reduces the hypertensive response to air‐jet stress

Ufnal

Drapała

Sikora

et al. 2012

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Brain angiotensin (Ang) II and vasopressin play important roles in the neurogenic regulation of the circulatory system, such as in cardiovascular responses to stress. Recently, it has become evident that the positive effects of statins are not limited to their lipid-lowering actions; for example, it has been found that statins interact with angiotensin peptides. In the present study we tested the hypothesis that simvastatin affects haemodynamic responses to air-jet stress and intracerebroventricular infusions of vasopressin and AngII. We maintained 12-week-old male Sprague-Dawley rats either on tap water (control) or on water containing simvastatin (20, 40 or 60 mg/L) for 4 weeks. Subsequently, we measured arterial blood pressure and heart rate (HR) at baseline and after air-jet stress or intracerebroventricular infusions over 30 s of 10 ng AngII, 20 ng vasopressin or their antagonists (10 μg losartan and 400 ng d(CH(2) )(5) [Tyr(Me)(2) ,Ala-NH(2) (9) ] vasopressin, respectively). There were no significant differences between the control and simvastatin groups in terms of baseline mean arterial blood pressure (MAP) and HR. In rats given 60 mg/L simvastatin, the hypertensive response to air-jet stress was significantly smaller than in controls, as was the increase in MAP in response to AngII. In contrast, there was no significant difference between the groups in terms of the hypertensive response to vasopressin. These findings show that simvastatin affects the hypertensive response to air-jet stress and provide evidence that statins may affect the brain's regulation of the circulatory system.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Oral simvastatin reduces the hypertensive response to air‐jet stress

Ufnal

Drapała

Sikora

et al. 2012

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…Circulating Ang II stimulates production and release of adrenal aldosterone, and an increase in hypothalamic aldosterone may also reflect uptake from the circulation, 12 despite its poor penetration. 13 Direct central infusion of Ang II also causes sympathetic hyperactivity 14 and hypertension, 14,15 and may be a more specific stimulus for CNS aldosterone synthesis.…”

mentioning

confidence: 99%

Role of Brain Corticosterone and Aldosterone in Central Angiotensin II–Induced Hypertension

et al. 2013

View full text Add to dashboard Cite

Abstract-Circulating angiotensin II (Ang II) activates a central aldosterone-mineralocorticoid receptor neuromodulatory pathway, which mediates most of the Ang II-induced hypertension. This study examined whether specific central infusion of Ang II also activates this central aldosterone-mineralocorticoid receptor pathway. Intracerebroventricular infusion of Ang II at 1.0, 2.5, and 12.5 ng/min for 2 weeks caused dose-related increases in water intake, Ang II concentration in the cerebrospinal fluid, and blood pressure. Intracerebroventricular Ang II, at 2.5 and 12.5 ng/min, increased hypothalamic aldosterone and corticosterone, as well as plasma aldosterone and corticosterone without affecting plasma Ang II levels. Intracerebroventricular infusion of the aldosterone synthase inhibitor FAD286-but not the mineralocorticoid receptor blocker eplerenone-inhibited by ≈60% the Ang II-induced increase in hypothalamic aldosterone. Both blockers attenuated by ≈50% the increase in plasma aldosterone and corticosterone with only minimal effects on hypothalamic corticosterone. By telemetry, intracerebroventricular infusion of Ang II maximally increased blood pressure within the first day with no further increase over the next 2 weeks.

show abstract