Acute simvastatin treatment restores cerebral functional capillary density and attenuates angiotensin <scp>II</scp>‐induced microcirculatory changes in a model of primary hypertension

Freitas, Felipe; Estato, Vanessa; Reis, Patrícia Alves; Castro‐Faria‐Neto, Hugo C.; Carvalho, Vinícius Frias; Torres, Rafael Carvalho; Lessa, Marcos Adriano; Tibiriçá, Eduardo

doi:10.1111/micc.12416

Cited by 13 publications

(25 citation statements)

References 88 publications

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“…On the other hand, measuring LSCI perfusion is easy, noninvasive, and can be measured several times for long-term follow-up, even in small animal models such as mouse. LSCI has been used to determine microcirculation in several tissues such as in bowel lesions in neonates (Knudsen et al 2017), in brain to determine cerebral blood flow (Freitas et al 2017), in renal cortical perfusion (Mitrou et al 2016), retinal and skin perfusion (Senarathna et al 2013). Our immunostaining findings confirm endothelial dysfunction and fibrosis in the aging mouse penis.…”

Section: Discussionsupporting

confidence: 64%

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Characterization of age‐related penile microvascular hemodynamic impairment using laser speckle contrast imaging: possible role of increased fibrogenesis

Lee

Kim

You

et al. 2017

Physiological Reports

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Current technology for penile hemodynamic evaluations in small animals is invasive and has limitations. We evaluated a novel laser speckle contrast imaging (LSCI) technique to determine age‐related changes in penile microvascular perfusion (PMP) and tested the role of cavernosal muscle (CC) fibrosis mediated by Wnt‐TGF β1 signaling pathways in a mouse model. Ten young (2–3 months) and old (24–28 months) wild‐type C57BL6 male mice were subjected to PMP measured using a LSCI system. Penile blood flow (PBF, peak systolic velocity, PSV) was also measured using a color Doppler ultrasound for comparison. Measurements were made before and after injection of vasoactive drugs: prostaglandin E1 (PGE 1) and acetylcholine (ACh). CC was processed for immunohistochemical studies for markers of endothelium and fibrosis. Protein levels were quantified by Western blot.PMP and PBF increased significantly from baseline after injection of vasoactive drugs. Peak PMP after PGE 1 and ACh was higher in young mice (225.0 ± 12.0 and 211.3 ± 12.1 AU) compared to old (155.9 ± 7.1 and 162.6 ± 5.1 AU, respectively). PSV after PGE 1 was higher in young than old mice (112.7 ± 8.5 vs. 78.2 ± 4.6 mm/sec). PSV after ACh was also higher in young (112.7 ± 5.6 mm/sec) than older mice (69.2 ± 7.1 mm/sec). PMP positively correlated with PSV (r = 0.867, P = 0.001). Immunostaining and Western blot showed increased protein expression of all fibrosis markers with aging. LSCI is a viable technique for evaluating penile hemodynamics. Increased cavernosal fibrosis may cause impaired penile hemodynamics and increased incidence of erectile dysfunction in older men.

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Section: Discussionsupporting

confidence: 64%

“…), in brain to determine cerebral blood flow (Freitas et al. ), in renal cortical perfusion(Mitrou et al. ), retinal and skin perfusion (Senarathna et al.…”

Section: Discussionmentioning

confidence: 99%

Characterization of age‐related penile microvascular hemodynamic impairment using laser speckle contrast imaging: possible role of increased fibrogenesis

Lee

Kim

You

et al. 2017

Physiological Reports

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“…It should be mentioned that in addition to hypertension treatment, hypolipidemic medications and statins in particular seem to have a beneficial effect on microcirculation even during acute administration; this is recognized as an additional pleiotropic effect of statins.…”

Section: Effects Of Antihypertensive Treatment On Microvascular Dysfumentioning

confidence: 99%

“…Intervention Summary of main findings Boegehold 28 Dahl salt-sensitive rats High-or low-salt diets for 4 wk High-salt intake reduced the passive diameter of large arterioles by 20% and was associated with increased tone of proximal, but not distal, arterioles It should be mentioned that in addition to hypertension treatment, hypolipidemic medications and statins in particular seem to have a beneficial effect on microcirculation even during acute administration 48 ; this is recognized as an additional pleiotropic effect of statins.…”

Section: Animal Modelmentioning

confidence: 99%

Salt‐induced effects on microvascular function: A critical factor in hypertension mediated organ damage

Marketou

Maragkoudakis

Anastasiou

et al. 2019

J of Clinical Hypertension

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Salt has been linked very closely to the occurrence and complications of arterial hypertension. A large percentage of patients with essential hypertension are salt‐sensitive; that is, their blood pressure increases with increased salt intake and decreases with its reduction. For this reason, emphasis is placed on reducing salt intake to better regulate blood pressure. In day‐to‐day clinical practice this is viewed as mandatory for hypertensive patients who are judged to be salt‐sensitive. Previous studies have highlighted the negative effect of high‐salt diets on macrovascular function, which also affects blood pressure levels by increasing peripheral resistances. More recent studies provide a better overview of the pathophysiology of microvascular disorders and show that they are largely due to the overconsumption of salt. Microvascular lesions, which have a major impact on the functioning of vital organs, are often not well recognized in clinical practice and are not paid sufficient attention. In general, the damage caused by hypertension to the microvascular network is likely to be overlooked, while reversion of the damage is only rarely considered as a therapeutic target by the treating physician. The purpose of this review is to summarize the impact and the harmful consequences of increased salt consumption in the microvascular network, their significance and pathophysiology, and at the same time to place some emphasis on their treatment and reversion, mainly through diet.

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“…Genetic and pharmacological approaches have demonstrated that angiotensin II can trigger vasoconstriction or vasodilation via AT1 receptors or dilation through AT2 receptors located in the endothelium and smooth muscle cells of cerebral microvessels (Haberl et al 1990;Meng and Busija 1993;Baranov and Armstead 2005;Vincent et al 2005;Wackenfors et al 2006;Zhou et al 2006;De Silva and Faraci 2012;Freitas et al 2017). Human brain pericytes also express both the AT1 and AT2 receptors (Kuroda et al 2014;Fig.…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

The role of pericytes in brain disorders: from the periphery to the brain

Hirunpattarasilp

Attwell

Freitas

2019

Journal of Neurochemistry

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It is becoming increasingly apparent that disorders of the brain microvasculature contribute to many neurological disorders. In recent years it has become clear that a major player in these events is the capillary pericyte which, in the brain, is now known to control the blood–brain barrier, regulate blood flow, influence immune cell entry and be crucial for angiogenesis. In this review we consider the under‐explored possibility that peripheral diseases which affect the microvasculature, such as hypertension, kidney disease and diabetes, produce central nervous system (CNS) dysfunction by mechanisms affecting capillary pericytes within the CNS. We highlight how cellular messengers produced peripherally can act via signalling pathways within CNS pericytes to reshape blood vessels, restrict blood flow or compromise blood–brain barrier function, thus causing neuronal dysfunction. Increased understanding of how renin–angiotensin, Rho‐kinase and PDGFRβ signalling affect CNS pericytes may suggest novel therapeutic approaches to reducing the CNS effects of peripheral disorders.

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Acute simvastatin treatment restores cerebral functional capillary density and attenuates angiotensin II‐induced microcirculatory changes in a model of primary hypertension

Abstract: The antihypertensive effect of SIM is associated with an improvement in cerebral microvascular perfusion and capillary density that may help to prevent hypertension-induced cerebrovascular damage independent of cholesterol-lowering.

Cited by 13 publications

References 88 publications

Characterization of age‐related penile microvascular hemodynamic impairment using laser speckle contrast imaging: possible role of increased fibrogenesis

Characterization of age‐related penile microvascular hemodynamic impairment using laser speckle contrast imaging: possible role of increased fibrogenesis

Salt‐induced effects on microvascular function: A critical factor in hypertension mediated organ damage

The role of pericytes in brain disorders: from the periphery to the brain

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