Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect

Carneado, J; Sotomayor, Marı́a Álvarez de; Pérez‐Guerrero, Concepción; Jiménez, Luís; Herrera, Marcelino; Pamies, E.; Martin-Sanz, Maria D V; Stiefel, Pablo; Miranda, M. DiCiero; Bravo, Luis Eduardo; Marhuenda, E.

doi:10.1097/00004872-200203000-00018

Cited by 61 publications

(54 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…26 Recent in vivo 27,28 and in vitro 29,30 studies have shown that fluvastatin has more potent antioxidative effects than other statins, including pravastatin, simvastatin, cerivastatin, and atorvastatin, although simvastatin also has some antioxidant effect. 31 Thus, the powerful antioxidant properties of fluvastatin may have contributed to the reduction in PWV.…”

Section: Discussionmentioning

confidence: 99%

Long-term effects of statins on arterial pressure and stiffness of hypertensives

et al. 2004

View full text Add to dashboard Cite

Although lowering blood pressure (BP) reduces aortic stiffness, achieving the recommended BP goal can be difficult. Recent studies have shown that short-term use of statins can reduce BP significantly. To determine the long-term effects of statins on BP and aortic stiffness, a single-blind randomized prospective study was performed on 85 hyperlipidaemic hypertensive patients whose BP was insufficiently controlled by antihypertensive therapy. Every 3 months, aortic stiffness was assessed by measuring pulse wave velocity (PWV). Patients were randomly allocated to groups treated with pravastatin, simvastatin, fluvastatin, or a nonstatin antihyperlipidaemic drug. No significant differences in patient characteristics, kinds of antihypertensive drugs, BP, ankle brachial index, PWV, or serum lipid, creatinine, or C-reactive protein levels were found between the four groups at the start of the study. During the 12-month treatment period, PWV did not change in the pravastatin group or nonstatin group, but it was transiently reduced in the simvastatin group and significantly decreased in the fluvastatin group, even though the doses of the statins used in this study were lower than the usually prescribed dose. All four antihyperlipidaemic drugs significantly decreased serum cholesterol levels without affecting BP, ankle brachial index, or serum triglyceride levels. The Creactive protein serum levels decreased significantly in the three statin groups but not in the nonstatin group. These results suggest that long-term use of fluvastatin by hyperlipidaemic hypertensive patients is associated with a significant reduction in aortic stiffness without any effect on BP.

show abstract

Section: Discussionmentioning

confidence: 99%

Long-term effects of statins on arterial pressure and stiffness of hypertensives

et al. 2004

View full text Add to dashboard Cite

show abstract

“…It is likely that the ability of aspirin not to interfere with the synthesis of PGI 2 and its ability to enhance NO production and/or its half-life by decreasing oxidative stress could be responsible for its beneficial actions. These results (Carneado et al, 2002;El Midaoui et al, 2002) suggest that the balance between O 2 ÀK , NO, and PGI 2 is critical in the prevention of hypertension.…”

Section: Introductionmentioning

confidence: 87%

“…The role of O 2 ÀK in hypertension is not without controversy. For instance, simvastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, used in the management of hyperlipidemias is known to behave like an anti-oxidant: simvastatin increases the activities of SOD and glutathione peroxidase and thus improves endothelial function (Carneado et al, 2002). No reduction in the increased blood pressure was noted in simvastatin-treated SHR, and subjects with hypertension, suggesting that O 2 ÀK may not always be responsible for hypertension.…”

Section: Introductionmentioning

confidence: 99%

“…No reduction in the increased blood pressure was noted in simvastatin-treated SHR, and subjects with hypertension, suggesting that O 2 ÀK may not always be responsible for hypertension. In several of these animal and human studies (Carneado et al, 2002), concentrations of NO were not measured. It is likely that failure of simvastatin to restore the concentrations of NO to normalcy could explain their inability to reduce hypertension.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

Das¹

2004

Eur J Clin Nutr

View full text Add to dashboard Cite

Patients with uncontrolled essential hypertension have elevated concentrations of superoxide anion (O 2 ÀK ), hydrogen peroxide (H 2 O 2 ), lipid peroxides, endothelin, and transforming growth factor-b (TGF-b) with a simultaneous decrease in endothelial nitric oxide (eNO), superoxide dismutase (SOD), vitamin E, and long-chain polyunsaturated fatty acids (LCPUFAs). Physiological concentrations of angiotensin II activate NAD(P)H oxidase and trigger free radical generation (especially that of O 2 ÀK ). Normally, angiotensin II-induced oxidative stress is abrogated by adequate production and release of eNO, which quenches O 2 ÀK to restore normotension. Angiotensin II also stimulates the production of endothelin and TGF-b. TGF-b enhances NO generation, which in turn suppresses TGF-b production. Thus, NO has a regulatory role on TGF-b production and is also a physiological antagonist of endothelin. Antihypertensive drugs suppress the production of O 2 ÀK and TGF-b and enhance eNO synthesis to bring about their beneficial actions. LCPUFAs suppress angiotensin-converting enzyme (ACE) activity, reduce angiotensin II formation, enhance eNO generation, and suppress TGF-b expression. Perinatal supplementation of LCPUFAs decreases insulin resistance and prevents the development of hypertension in adult life, whereas deficiency of LCPUFAs in the perinatal period results in raised blood pressure later in life. Patients with essential hypertension have low concentrations of various LCPUFAs in their plasma phospholipid fraction. Based on this, it is proposed that LCPUFAs serve as endogenous regulators of ACE activity, O 2 ÀK , eNO generation, and TGF-b expression. Further, LCPUFAs have actions similar to statins, inhibit (especially o-3 fatty acids) cyclooxygenase activity and suppress the synthesis of proinflammatory cytokines, and activate the parasympathetic nervous system, all actions that reduce the risk of major vascular events. Hence, it is proposed that availability of adequate amounts of LCPUFAs during the critical periods of growth prevents the development of hypertension in adulthood.

show abstract

“…Statins have antiinflammatory and anti-oxidant properties by their inhibition of neutrophil activity, reduction of oxidative stress, and maintenance of vascular integrity. [26][27][28] However, it still remains to be determined whether statin therapy, as well as ARB use, is correlated with peptic ulcer or NSAID-induced mucosal injuries in humans. …”

Section: Risk Factors For Upper Gi Bleedingmentioning

confidence: 99%

Risk and preventive factors of low‐dose aspirin‐induced gastroduodenal injuries: A comprehensive review

Shiotani

Manabe

Kamada

et al. 2012

J of Gastro and Hepatol

View full text Add to dashboard Cite

The risk of peptic ulcer complications, particularly bleeding, is increased in association with the use of low-dose aspirin (LDA). Risk factors for upper gastrointestinal (GI) ulcer or bleeding among LDA users include a history of prior GI events, older age, chronic renal failure, combined antithrombotic therapy and nonsteroidal anti-inflammatory drugs (NSAIDs). Helicobacter pylori and aspirin seem to be independent risk factors for peptic ulcer and bleeding. The studies report conflicting findings about the effect of H. pylori infection on NSAID-related ulcers, and proton-pump inhibitors (PPIs) seem to be superior to eradication only to prevent recurrent ulcer bleeding with LDA. Previous studies indicate that hypoacidity related to corpus atrophy, as well as taking PPIs and co-treatment with angiotensin type 1 receptor blockers (ARBs) and statins seem to reduce peptic ulcer among LDA users. In addition, the interleukin-1b (IL-1b)-511 T allele and angiotensinogen (AGT)-20 CC, which work as the high-producer allele of IL-1b and AGT, are significantly associated with ulcer or ulcer bleeding. The SLCO1B1*1b haplotype, which has the highest transport activity, may diminish the preventive effect of statins or ARBs. The data are still lacking and further prospective studies are needed to identify the specific risk or protective factors for upper GI ulcer and its complications associated with LDA.Key words angiotensin type 1 receptor blocker, angiotensinogen, aspirin, interleukin-1b, polymorphism, SLCO1B*1b, statins.

show abstract

Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect

Abstract: Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

Cited by 61 publications

References 31 publications

Long-term effects of statins on arterial pressure and stiffness of hypertensives

Long-term effects of statins on arterial pressure and stiffness of hypertensives

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

Risk and preventive factors of low‐dose aspirin‐induced gastroduodenal injuries: A comprehensive review

Contact Info

Product

Resources

About