Improvement in endothelial function by angiotensin-converting enzyme inhibition in non–insulin-dependent diabetes mellitus

O’Driscoll, Gerry; Green, Daniel; Maiorana, Andrew; Stanton, K.; Colreavy, Frances; Taylor, Roger R.

doi:10.1016/s0735-1097(99)00065-0

Cited by 165 publications

(110 citation statements)

References 38 publications

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“…The reasons for the increased risk are unclear but may be related to several abnormalities, the most prominent of which appears to be endothelial dysfunction (7). ACE inhibitors have been shown to have a beneficial effect on improving vascular reactivity (8). However, we have recently demonstrated that in African American patients with proteinuria that persists despite optimal ACE inhibitor therapy, endothelial function is severely impaired compared to both matched patients whose proteinuria resolved as well as similarly affected Non-Hispanic whites .…”

Section: Introductionmentioning

confidence: 97%

Beta-blockers have a beneficial effect upon endothelial function and microalbuminuria in African-American subjects with diabetes and hypertension

Jawa

Nachimuthu

Pendergrass

et al. 2008

Journal of Diabetes and its Complications

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Background-Type-2 Diabetes Mellitus(T2DM) with microalbuminuria(MA) is associated with increased risk of cardiovascular events(CVE) that may be attenuated by Angiotensin-ConvertingEnzyme Inhibitors(ACEIs), unless microalbuminuria persists(PMA). African-Americans(AA) have a higher prevalence of nephropathy with suboptimal response to ACEIs. We studied the effects of beta-blockers addition and comparative effects of carvedilol with metoprolol on 24-hour urinaryalbumin excretion(UAE) and endothelial function(EF) in AA with PMA.

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Section: Introductionmentioning

confidence: 97%

Beta-blockers have a beneficial effect upon endothelial function and microalbuminuria in African-American subjects with diabetes and hypertension

Jawa

Nachimuthu

Pendergrass

et al. 2008

Journal of Diabetes and its Complications

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“…Over the past several years, a number of studies have implicated an important role for the renin-angiotensin system in the pathogenesis of cardiovascular abnormalities associated with T1D. For example, investigators have shown that tissue and plasma levels of angiotensin converting enzyme (ACE) and angiotensin II are elevated in diabetic subjects and animals (Duntas et al, 1992;HarrisonBernard et al, 2002;Lieberman and Sastre, 1980;Schernthaner et al, 1984) and treatment of diabetic subjects with ACE inhibitors can improve impaired NOS-dependent responses of large peripheral vessels (Arcaro et al, 1999;Cheetham et al, 2000;O'Driscoll et al, 1997;O'Driscoll et al, 1999). In addition, we (Trauernicht et al, 2003) have shown that treatment of diabetic rats with an ACE inhibitor (enalapril) could alleviate impaired eNOS-dependent responses of cerebral arterioles during T1D.…”

Section: Introductionmentioning

confidence: 99%

Losartan improves impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type 1 diabetic rats

et al. 2008

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We examined whether activation of angiotensin-1 receptors (AT1R) could account for impaired responses of cerebral arterioles during Type 1 diabetes (T1D). First, we measured responses of cerebral arterioles in nondiabetic rats to eNOS-dependent (acetylcholine and adenosine diphosphate (ADP)) and -independent (nitroglycerin) agonists before and during application of angiotensin II. Next, we examined whether losartan could improve impaired responses of cerebral arterioles during T1D. In addition, we harvested cerebral microvessels for Western blot analysis of AT1R protein and measured production of superoxide anion by brain tissue under basal conditions and in response to angiotensin II in the absence or presence of losartan. We found that angiotensin II specifically impaired eNOS-dependent reactivity of cerebral arterioles. In addition, while losartan did not alter responses in nondiabetics, losartan restored impaired eNOS-dependent vasodilatation in diabetics. Further, AT1R protein was higher in diabetics compared to nondiabetics. Finally, superoxide production was higher in brain tissue from diabetics compared to nondiabetics under basal conditions, angiotensin II increased superoxide production in nondiabetics and diabetics, and losartan decreased basal (diabetics) and angiotensin II-induced production of superoxide (nondiabetics and diabetics). We suggest that activation of AT1R during T1D plays a critical role in impaired eNOS-dependent dilatation of cerebral arterioles.

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“…Angiotensin-converting enzyme inhibition improves both of these prognostic markers in diabetes [13,14] and is also associated with an improvement in morbidity and mortality in diabetic subjects [15]. It is thought that ACE inhibitors beneficially affect these parameters by reducing angiotensin II bioactivity [16,17].…”

Section: Introductionmentioning

confidence: 99%

Spironolactone impairs endothelial function and heart rate variability in patients with Type 2 diabetes

et al. 2004

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Aims/hypothesis. Aldosterone blockade has followed in the footsteps of ACE inhibition in reducing mortality in patients with heart failure. This is associated with its beneficial effects on endothelial function and heart rate variability. Diabetes is another area, where angiotensin II withdrawal has proven to be of particular value. We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients. Methods. We assessed endothelial function by forearm venous occlusion plethysmography in 42 patients with Type 2 diabetes mellitus after 1 month of treatment with spironolactone or placebo allocated in a randomised double-blind trial. Of the 42 patients, 20 were on ACE inhibitor therapy. We also assessed heart rate variability, HbA 1 c and plasma angiotensin II levels at the end of each treatment period. Results. Compared to placebo, spironolactone decreased forearm blood flow response to acetylcholine by 44.56±14.56% (p=0.003) in the group as a whole and by 57.61±15.56% (p<0.001) in the 20 patients on ACE inhibition. Spironolactone also worsened heart rate variability parameters, with root mean squared standard deviation decreased by 1.99±0.93 ms (p=0.03), low-frequency normalised power increased by 2.00±0.91 normalised units (nu) (p=0.03), high-frequency normalised power decreased by 1.98±0.94 nu (p=0.04) and the low frequency : high frequency ratio increased by 0.40±0.19 (p=0.04). HbA 1 c and angiotensin II increased during treatment with spironolactone by 0.26±0.07% (p=0.001) and 8.12±1.94 pg/ml (p=0.001) respectively. Conclusions/interpretation. Spironolactone worsened endothelial function and heart rate variability in patients with Type 2 diabetes. These findings are possibly due to the worsening of glycaemic control and increase in plasma angiotensin II that were seen with spironolactone treatment. Thus the prescription of spironolactone to diabetic patients without heart failure does not seem to be justified.

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Improvement in endothelial function by angiotensin-converting enzyme inhibition in non–insulin-dependent diabetes mellitus

Abstract: In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.

Cited by 165 publications

References 38 publications

Beta-blockers have a beneficial effect upon endothelial function and microalbuminuria in African-American subjects with diabetes and hypertension

Beta-blockers have a beneficial effect upon endothelial function and microalbuminuria in African-American subjects with diabetes and hypertension

Losartan improves impaired nitric oxide synthase-dependent dilatation of cerebral arterioles in type 1 diabetic rats

Spironolactone impairs endothelial function and heart rate variability in patients with Type 2 diabetes

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