Effect of Enalapril on Endothelial Function in Young Insulin-Dependent Diabetic Patients: A Randomized, Double-Blind Study 11This study was supported by a grant from Merck Sharp and Dohme Ltd., Hertfordshire, England, United Kingdom. Ms. Donald is supported by a grant from the Coronary Artery Disease Research Foundation (CORDA), London, England, United Kingdom.

Mullen, Michael; Clarkson, Patrick; Donald, Ann; Thomson, Hyeyoung; Thorne, Sara; Powe, Amanda J.; Furuno, Takashi; Bull, Teresa; Deanfield, John

doi:10.1016/s0735-1097(98)00099-0

Cited by 67 publications

(4 citation statements)

References 43 publications

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“…In addition to effects on arterial stiffness, we observed significant positive effects on endothelial function. The effect of ACEI therapy on endothelial function is variable; in obese, nondiabetic human subjects, and in some studies involving subjects with type 1 diabetes, ACEIs had no effect on endothelial function (23,24). In hypertensive individuals, ACEIs improve flow-mediated dilatation by 30–40% (24).…”

Section: Discussionmentioning

confidence: 99%

Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes

et al. 2009

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OBJECTIVEBlockade of the renin-angiotensin system (RAS) plays an important role in preventing end-organ injury associated with diabetes. The recent development of direct renin inhibitors (DRIs) provides a new approach to block the RAS, but the effects of DRIs on renal and systemic vascular function in uncomplicated type 1 diabetes have not been elucidated.RESEARCH DESIGN AND METHODSRenal hemodynamic function (inulin and paraaminohippurate clearance), augmentation index and pulse wave velocity, endothelial dependent vasodilatation (flow-mediated dilation [FMD]), and endothelial independent vasodilatation (response to sublingual nitroglycerin) were evaluated before and after administration of aliskiren (300 mg daily for 30 days) in 10 adult subjects with uncomplicated type 1 diabetes during clamped euglycemia (4–6 mmol/l) and hyperglycemia (9–11 mmol/l).RESULTSIn response to the DRI, plasma renin activity decreased (from 0.40 to 0.13 ng · ml−1 · h−1, P < 0.05) and plasma renin increased (from 5.2 to 75.0 ng/l, P < 0.05). Peripheral and central blood pressures decreased, and effective renal plasma flow and glomerular filtration rate increased during clamped euglycemia and hyperglycemia (P < 0.05). The carotid augmentation index during clamped euglycemia decreased (from 26 ± 6 to 20 ± 5%, P < 0.05) as did pulse wave velocity during clamped hyperglycemia (from 7.8 ± 0.6 to 6.8 ± 0.5 m/s, P < 0.05). In response to the DRI, FMD increased during both clamped euglycemia (from 1.92 ± 1.13 to 5.55 ± 0.81%) and hyperglycemia (from 1.86 ± 0.98 to 5.63 ± 0.62) as did the vasodilatory response to sublingual nitroglycerin.CONCLUSIONSDRIs exert a renal vasodilatory effect and improve parameters of systemic vascular function, suggesting that blockade of the RAS with this new class of agents has important functional effects in subjects with uncomplicated type 1 diabetes.

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Section: Discussionmentioning

confidence: 99%

Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes

et al. 2009

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“…Improvement in endothelium-dependent vasodilation with ACE inhibition in patients with IDDM was found in two studies [94,95], but these findings were not obtained in three studies (i.e., an ACE inhibitor did not alter endothelium-dependent vasodilation.) [96][97][98]. The reason for these discrepancies remains unclear.…”

Section: -2 Effects Of Arbs On Endothelial Function In Patients Witmentioning

confidence: 99%

Angiotensin II Type I Receptor Blocker and Endothelial Function in Humans: Role of Nitric Oxide and Oxidative Stress

Higashi

Chayama²,

Yoshizumi

2005

CMCCHA

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Recent large clinical trials have shown that angiotensin II type I receptor blockers (ARBs) reduce cardiovascular morbidity and mortality in patients with heart failure, acute myocardial infarction, and hypertension. However, the mechanism underlying antiatherogenic effects of ARBs remains unclear. The vascular endothelium is involved in the release of various vasodilators, including nitric oxide (NO), prostacyclin, and endothelium-derived hyperpolarizing factor as well as vasoconstrictors. NO plays an important role in the regulation of vascular tone, the inhibition of platelet aggregation, and the suppression of smooth muscle cell proliferation. Several investigators have reported impairment in endothelium-dependent vasodilation in the forearm, coronary, and renal vasculature in cardiovascular diseases, including hypertensive patients. Cardiovascular diseases are associated with alteration in endothelial function. Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis. Anti-renin-angiotensin system agents, angiotensin-converting enzyme (ACE) inhibitors improve endothelial function in patients with hypertension, diabetes mellitus, and coronary artery disease. It is well known that ACE inhibitors augment endothelium-dependent vasodilation through an increase in NO bioavailability, by an increase in NO production and a decrease in NO inactivation. ARBs are also thought to prevent cardiovascular complications through an augmentation of endothelial function. In this review, we focus on recent findings and putative mechanisms of the beneficial effects of ARBs on endothelial function.

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“…Valsartan therapy improved resting forearm skin blood flow and resting brachial artery diameter after 12 weeks in patients with type 2 diabetes. However, their impact on endothelial function in patients with type 1 diabetes is less clear (113–116). ACE inhibitors and ARBs improve cardiovascular and all-cause mortality outcomes in patients with diabetes, in fact, to a greater degree than in non-diabetics as noted in subgroup analysis of the HOPE and LIFE studies (approx 38% and 19%, respectively, of subjects had diabetes) (117, 118).…”

Section: Therapeutic Interventions That Modify Oxidative Stressmentioning

confidence: 99%

Therapeutic interventions and oxidative stress in diabetes

Rahangdale

Yeh²,

Malhotra³

et al. 2009

Front Biosci

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Many therapeutic agents that are used in patients with diabetes mitigate oxidative stress. These agents are of particular interest because oxidative stress is elevated in diabetes and is thought to contribute to vascular dysfunction. Agents that merely quench already formed reactive oxygen species have demonstrated limited success in improving cardiovascular outcomes. Thus, although vitamin E, C, and alpha lipoic acid appeared promising in animal models and initial human studies, subsequent larger trials have failed to demonstrate improvement in cardiovascular outcomes. Drugs that limit the production of oxidative stress are more successful in improving vascular outcomes in patients with diabetes. Thus, although statins, ACE inhibitors, ARBs and thiazolinediones are used for varied clinical purposes, their increased efficacy in improving cardiovascular outcomes is likely related to their success in reducing the production of reactive oxygen species at an earlier part of the cascade, thereby more effectively decreasing the oxidative stress burden. In particular, statins and ACE inhibitors/ARBs appear the most successful at reducing oxidative stress and vascular disease and have potential for synergistic effects.

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Cited by 67 publications

References 43 publications

Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes

Effect of Direct Renin Inhibition on Renal Hemodynamic Function, Arterial Stiffness, and Endothelial Function in Humans With Uncomplicated Type 1 Diabetes

Angiotensin II Type I Receptor Blocker and Endothelial Function in Humans: Role of Nitric Oxide and Oxidative Stress

Therapeutic interventions and oxidative stress in diabetes

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