Endothelium as a Therapeutic Target in Heart Failure

Drexler, Helmut

doi:10.1161/01.cir.98.24.2652

Cited by 113 publications

(75 citation statements)

References 47 publications

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“…Indeed, improving endothelial dysfunction has recently been suggested as a new therapeutic target in CHF. 13 Spironolactone appears to be a treatment that not only achieves that target but also reduces total mortality in patients with heart failure.…”

Section: Discussionmentioning

confidence: 99%

Spironolactone Increases Nitric Oxide Bioactivity, Improves Endothelial Vasodilator Dysfunction, and Suppresses Vascular Angiotensin I/Angiotensin II Conversion in Patients With Chronic Heart Failure

2000

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Background-The RALES study showed that spironolactone, added to conventional therapy for chronic heart failure, dramatically reduced mortality. We tested the hypothesis that this benefit was partially due to improvement in endothelial function and/or to amplified suppression of the vascular renin-angiotensin axis. Methods and Results-We performed a randomized, placebo-controlled, double-blind crossover study on 10 patients with NYHA class II to III chronic heart failure on standard diuretic/ACE inhibitor therapy, comparing 50 mg/d spironolactone (1 month) versus placebo. Forearm vasculature endothelial function was assessed by bilateral forearm venous occlusion plethysmography using acetylcholine and

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Section: Discussionmentioning

confidence: 99%

Spironolactone Increases Nitric Oxide Bioactivity, Improves Endothelial Vasodilator Dysfunction, and Suppresses Vascular Angiotensin I/Angiotensin II Conversion in Patients With Chronic Heart Failure

2000

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“…Retrospective analysis of the large statin trials, such as the 4S, suggests that statins reduce the incidence and morbidity of heart failure (148). Second, patients with heart failure are characterized by increased vascular tone and endothelial dysfunction (149), which may be improved by statin therapy, irrespective of serum cholesterol levels. Third, statins have proven to preserve cardiac function in animal models of myocardial hyper-trophy and heart failure, such as aortic banding, myocardial infarction, and several transgenic models (145,(150)(151)(152).…”

Section: Effects Of Statins On the Myocardiummentioning

confidence: 99%

Pleiotropic Effects of Statins

Liao

Laufs

2005

Annu. Rev. Pharmacol. Toxicol.

1,612

1,198

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Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or "pleiotropic" effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

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“…Finally, and more importantly, the beneficial effect of chronic BK infusion on myocardial function and hemodynamics may be related to a preserved NO-mediated endothelial function. It is known that endothelial dysfunction occurs in HF 20 and ACE inhibitors improve endothelial dysfunction. 7,8,21,22 Some studies showed that this effect of ACE inhibitors is BKmediated.…”

Section: Tonduangu Et Al Chronic Effects Of Bradykinin In Heart Failurementioning

confidence: 99%

Chronic Infusion of Bradykinin Delays the Progression of Heart Failure and Preserves Vascular Endothelium-Mediated Vasodilation in Conscious Dogs

et al. 2004

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Background-This study examined the effects of chronic bradykinin infusion on hemodynamics and myocardial and endothelial functions during the development of heart failure. Methods and Results-Sixteen instrumented dogs were randomized to receive through the left atria either vehicle or bradykinin (1 g/min) during ventricular pacing (250 bpm, 5 weeks). Hemodynamic and left ventricular (LV) parameters and the vasodilator responses to intravenous acetylcholine (0.3 to 3 g/kg) and nitroglycerin (1 to 10 g/kg) were examined in the control and after 3 and 5 weeks of pacing. The expression of endothelial NOS in femoral, carotid, and renal arteries was determined by Western blot analysis. After 3 weeks of pacing, changes in LV diastolic and systolic parameters were significantly lower in bradykinin-treated than vehicle-treated dogs (LV end-diastolic pressure, ϩ10Ϯ3 versus ϩ19Ϯ2 mm Hg; time constant of LV isovolumic relaxation, ϩ11Ϯ2 versus ϩ17Ϯ1 ms; LV wall thickening, Ϫ33Ϯ18% versus Ϫ75Ϯ9%; and cardiac output, Ϫ16Ϯ6% versus Ϫ32Ϯ6%; all PϽ0.05). Compared with vehicle-treated dogs, bradykinin-treated dogs had a reduced rightward shift of the diastolic LV pressure-diameter relation and a reduced diastolic LV wall stress. Similar trends were observed after 5 weeks. The vasodilator response to nitroglycerin was preserved in both groups. The response to acetylcholine was blunted in vehicle-treated but preserved in bradykinin-treated dogs. Vascular endothelial NOS expression decreased in vehicle-treated but was preserved in bradykinin-treated dogs. Conclusions-In

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Endothelium as a Therapeutic Target in Heart Failure

Cited by 113 publications

References 47 publications

Spironolactone Increases Nitric Oxide Bioactivity, Improves Endothelial Vasodilator Dysfunction, and Suppresses Vascular Angiotensin I/Angiotensin II Conversion in Patients With Chronic Heart Failure

Spironolactone Increases Nitric Oxide Bioactivity, Improves Endothelial Vasodilator Dysfunction, and Suppresses Vascular Angiotensin I/Angiotensin II Conversion in Patients With Chronic Heart Failure

Pleiotropic Effects of Statins

Chronic Infusion of Bradykinin Delays the Progression of Heart Failure and Preserves Vascular Endothelium-Mediated Vasodilation in Conscious Dogs

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