Effects of anti-hypertensive drugs on vessel rarefaction

Battegay, Edouard; Miguel, Lourdes Sánchez de; Petrimpol, Marco; Humar, Rok

doi:10.1016/j.coph.2006.09.007

Cited by 50 publications

(37 citation statements)

References 74 publications

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“…Some preclinical and clinical evidence supports the idea that angiotensin converting enzyme inhibitors (ACEi), which favor BK bioactivity by reducing its metabolism, may have a positive impact on the prevention or reversal of the microvascular structural rarefaction occurring in the abovementioned angiopathic diseases (Pellacani et al, 1994;Liu et al, 1997;Duncan et al, 2000;Feihl et al, 2006;Battegay et al, 2007). Vasculoprotective effects of ACEi seem to be mediated by mechanisms that are partly independent of their blood pressure lowering effects (Feihl et al, 2006;Battegay et al, 2007). Angiotensin II type 1 receptor (AT1) antagonists (ARA) may also mediate part of their beneficial pro-survival effects on ECs, possibly through increased BK formation (Matsumoto et al, 2003;Campbell et al, 2005;Battegay et al, 2007).…”

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confidence: 98%

“…Vasculoprotective effects of ACEi seem to be mediated by mechanisms that are partly independent of their blood pressure lowering effects (Feihl et al, 2006;Battegay et al, 2007). Angiotensin II type 1 receptor (AT1) antagonists (ARA) may also mediate part of their beneficial pro-survival effects on ECs, possibly through increased BK formation (Matsumoto et al, 2003;Campbell et al, 2005;Battegay et al, 2007).…”

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confidence: 99%

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Bradykinin protects against brain microvascular endothelial cell death induced by pathophysiological stimuli

Bovenzi

Savard

Morin

et al. 2009

Journal Cellular Physiology

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The morphological and functional integrity of the microcirculation is compromised in many cardiovascular diseases such as hypertension, diabetes, stroke, and sepsis. Angiotensin converting enzyme inhibitors (ACEi), which are known to favor bradykinin (BK) bioactivity by reducing its metabolism, may have a positive impact on preventing the microvascular structural rarefaction that occurs in these diseases. Our study was designed to test the hypothesis that BK, via B2 receptors (B2R), protects the viability of the microvascular endothelium exposed to the necrotic and apoptotic cell death inducers H(2)O(2) and LPS independently of hemodynamics. Expression (RT-PCR and radioligand binding) and functional (calcium mobilization with fura-2AM, and p42/p44MAPK and Akt phosphorylation assays) experiments revealed the presence of functional B2R in pig cerebral microvascular endothelial cells (pCMVEC). In vitro results showed that the cytocidal effects of H(2)O(2) and LPS on pCMVEC were significantly decreased by a BK pretreatment (MTT and crystal violet tests, annexin-V staining/FACS analysis), which was countered by the B2R antagonist HOE 140. BK treatment coincided with enhanced expression of the cytoprotective proteins COX-2, Bcl-2, and (Cu/Zn)SOD. Ex vivo assays on rat brain explants showed that BK impeded (by approximately 40%) H(2)O(2)-induced microvascular degeneration (lectin-FITC staining). The present study proposes a novel role for BK in microvascular endothelial protection, which may be pertinent to the complex mechanism of action of ACEi explaining their long-term beneficial effects in maintaining vascular integrity.

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confidence: 98%

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confidence: 99%

Bradykinin protects against brain microvascular endothelial cell death induced by pathophysiological stimuli

Bovenzi

Savard

Morin

et al. 2009

Journal Cellular Physiology

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“…Yet, there are no studies documenting cerebral artery rarefaction in hypertensive patients although capillary rarefaction appears to be a regular complication with implications for deleterious end-organ damage apart from the brain [19,50] . Further experimental studies are needed to elucidate upon the possible involvement of cerebral vessel rarefaction in the hypertensive brain especially, since studies showed that pro-angiogenic and anti-hypertensive therapies enhanced vessel density [51,52] .…”

Section: Cerebrovascular Dysfunction During Csvd and Hypertension Andmentioning

confidence: 99%

Hypertension and the Brain: A Risk Factor for More Than Heart Disease

Meißner

2016

Cerebrovasc Dis

126

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Background: Cerebral small vessel disease (cSVD), a common risk factor for cognitive impairment, involves unspecific arteriopathy characterized by hypertrophy and endothelial dysfunction that alter cerebrovascular function and auto-regulation of cerebral blood flow (CBF). Microbleedings, subcortical lacunar infarctions and diffuse areas of white matter lesions resulting from vascular injury are associated with reduced cognitive function mostly characterized by difficulties in learning and retention, attention deficits, gait disorders or depression. In recent years, it has become evident that vascular risk factors contribute to the development of cSVD and associated vascular cognitive impairment (VCI). Among them, hypertension emerged as such a major modifiable risk factor since the brain presents an early target for organ damage due to changes in blood pressure (BP). Subsequently both high and, especially in the elderly, low BP have been linked to cognitive decline, which initiated controversial discussions about BP control as a potential therapeutic strategy to achieve optimal brain perfusion and thus, reduce the occurrence of cSVD and cognitive dysfunction. Yet, recent randomized controlled trials examined the impact of anti-hypertensive therapy on cognitive performance with conflicting results. Summary: In light of the current knowledge, it becomes apparent that there is an urgent need to understand the mechanisms underlying hypertension-induced cerebrovascular complications in order to identify effective therapeutic targets to prevent and most importantly also reverse cognitive decline mediated through hypertension. Key Message: This review summarizes the current knowledge of cSVD pathogenesis as well as possible links to hypertension-mediated cerebrovascular complications. By pointing out knowledge gaps, it aims to spur future studies in search of specific targets helping to prevent therapy failures and decelerate the rapidly progressing neuro-degeneration of patients suffering from cerebrovascular diseases emanating from hypertension.

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“…Interestingly, capillary rarefaction is even present in normotensive men with a hypertensive disposition [4] and correlates inversely with insulin resistance in nondiabetic men [5], thereby suggesting a causal involvement in the precipitation of both diseases. Pathomechanisms of metabolic syndrome such as an increased demand of vascular perfusion pressure and an impairment of metabolite exchange may well be attributed to capillary rarefaction which is therefore considered as a promising target of therapy [6,7,8]. …”

Section: Introductionmentioning

confidence: 99%

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

Ashoff¹,

Qadri

Eggers

et al. 2012

J Vasc Res

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Background/Aims: Reduction of capillary network density occurs early in the development of metabolic syndrome and may be relevant for the precipitation of diabetes. Agonists of the peroxisome proliferator-activated receptor (PPAR)-γ transcription factor are vasculoprotective, but their capacity for structural preservation of the microcirculation is unclear. Methods: Male Wistar rats were rendered diabetic by streptozotocin and treated with pioglitazone in chow for up to 12 weeks. Capillary density was determined in heart and skeletal muscle after platelet endothelial cell adhesion molecule-1 (PECAM-1) immunostaining. Hallmarks of apoptosis and angiogenesis were determined. Results: Capillary density deteriorated progressively in the presence of hyperglycemia (from 971/mm² to 475/mm² in quadriceps muscle during 13 weeks). Pioglitazone did not influence plasma glucose, left ventricular weight, or body weight but nearly doubled absolute and relative capillary densities compared to untreated controls (1.2 vs. 0.6 capillaries/myocyte in heart and 1.5 vs. 0.9 capillaries/myocyte in quadriceps muscle) after 13 weeks of diabetes. No antiapoptotic or angiogenic influence of pioglitazone was detected while a reduced expression of hypoxia-inducible factor-3α and PPAR coactivator-1α (PGC-1α) mRNA as well as vascular endothelial growth factor (VEGF) protein possibly occurred as a consequence of improved vascularization. Conclusion: Pioglitazone preserves microvascular structure in diabetes independently of improvements in glycemic control and by a mechanism unrelated to VEGF-mediated angiogenesis.

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Effects of anti-hypertensive drugs on vessel rarefaction

Cited by 50 publications

References 74 publications

Bradykinin protects against brain microvascular endothelial cell death induced by pathophysiological stimuli

Bradykinin protects against brain microvascular endothelial cell death induced by pathophysiological stimuli

Hypertension and the Brain: A Risk Factor for More Than Heart Disease

Pioglitazone Prevents Capillary Rarefaction in Streptozotocin-Diabetic Rats Independently of Glucose Control and Vascular Endothelial Growth Factor Expression

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