Endothelium‐dependent Responses and Inhibition of Angiotensin‐converting Enzyme

Vanhoutte, Paul M.

doi:10.1111/j.1440-1681.1996.tb03037.x

Cited by 10 publications

(8 citation statements)

References 55 publications

(12 reference statements)

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“…ACE-I also limits bradykinin degradation, which may play a role in modulating endothelium-dependent relaxing factors. 27 Although not measured in our study, it seems possible that bradykinin levels may be increased both in the plasma and tissue of the subjects homozygous for the ACE I allele. A role for bradykinin modulation of pulmonary function is also implied from studies that suggest that salicylate (prostaglandin inhibitor) used in conjunction with ACE inhibitors adversely effects the alveolar-capillary membrane and gas exchange of patients with CHF.…”

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confidence: 65%

Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure

et al. 2002

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Background-The gene encoding ACE exhibits an insertion/deletion polymorphism resulting in 3 genotypes (DD, ID, and II), which affects serum and tissue ACE activity as well as other vasoactive substances. Pulmonary function is frequently abnormal in patients with congestive heart failure (CHF), the mechanism of which has not been completely characterized. ACE inhibition has been shown to improve diffusion across the alveolar-capillary membrane and to improve exercise capacity and gas exchange in CHF. The aim of the current study was to determine if ACE genotype is associated with altered pulmonary function and exercise intolerance in patients with treated CHF. Methods and Results-Fifty-seven patients (stratified according to ACE genotype as17 DD, 28 ID, 12 II) with ischemic and dilated cardiomyopathy, left ventricular ejection fraction (LVEF) Ͻ35%, and Ͻ10 pack-years of smoking history were studied. All patients were receiving standard therapy for left ventricular systolic dysfunction. Pulmonary function, LVEF, serum ACE, plasma angiotensin II, atrial natriuretic peptide, and brain natriuretic peptide were measured at baseline. Peak V O 2 and gas exchange measurements were assessed with graded exercise. Resting LVEF was similar among the genotype groups (25% to 28%), and no differences were observed in diastolic function or pulmonary artery pressures (PϾ0.05). Mean peak V O 2 and forced vital capacity (% Pred) were significantly reduced (PϽ0.05), whereas mean serum ACE activity and plasma angiotensin II concentration were highest in DD homozygotes. Subjects homozygous for the D-allele also demonstrated higher mean ventilatory equivalents for carbon dioxide (V E/V CO 2 ) during exercise (PϽ0.05). 4 -6 Baseline restrictive and obstructive pulmonary function changes as well as respiratory muscle weakness are common in CHF. 2,6 Guazzi et al 7 have shown that decreased lung diffusion and altered pulmonary vascular tone and permeability are associated with a reduced exercise capacity in CHF. We have recently demonstrated that patients with symptomatic CHF with markedly impaired exercise tolerance may approach ventilatory constraints as the result of reduced baseline lung volumes and flow rates as well as altered regulation of end-expiratory lung volume. 8 Impaired pulmonary function in CHF may be due to increased neurohumoral activation, particularly of the reninangiotensin system (RAS). Studies by Guazzi et al 9 have shown that ACE inhibition (ACE-I) restores alveolarcapillary permeability in patients with CHF, whereas use of hydralazine-isosorbide improves LV function without restoration of alveolar-capillary permeability, suggesting an independent modulating action of the RAS on pulmonary function. Conclusions-ACEACE genotype affects both serum and tissue ACE levels and the degree of neurohumoral activation associated with Methods Patient SelectionFifty-seven white patients (36 men, 19 women) with a diagnosis of CHF were recruited from the Heart Failure and Cardiovascular Health Clinics in the Division of Cardio...

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confidence: 65%

Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure

et al. 2002

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“…Recent studies have shown that reflex renal vasoconstriction is exaggerated in both magnitude and duration during dynamic exercise in HF patients (Middlekauff et al 2001; Momen et al 2004). In turn there is an increased activation of the renin-angiotensin system (Joyner 2004; Vanhoutte 1996) and an amplification of the already upregulated neurohumoral response seen in HF (Joyner 2004). Sinoway and Li (2005) showed that mechanically and chemically sensitive afferents in the exercising muscle are more likely to fire earlier and more often during dynamic exercise thereby amplifying the sympathetic nervous system response to exercise.…”

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confidence: 99%

Lung-to-lung circulation times during exercise in heart failure

et al. 2009

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Circulation time (the transit time for a bolus of blood through the circulatory system) is a potential index of cardiac dysfunction in chronic heart failure (HF). In healthy subjects, circulation time falls as cardiac output (Q) rises during exercise, however little is known about this index in HF. In this study we examined the relationship between lung-to-lung circulation time (LLCT) during exercise in ten HF (53 ± 14 year, resting ejection fraction = 23 ± 8%) and control subjects (51 ± 18 year). We hypothesized that HF patients would have slower LLCT times during exercise when compared to control subjects. Each subject completed two identical incremental exercise tests during which LLCT was measured in one test and Q measured in the other. Q was measured using the open circuit C2H2 washin technique and circulation time measured using an inert gas technique. In HF patients and control subjects, LLCT decreased and Q increased from rest (HF:LLCT = 53.6 ± 8.2 s, Q = 4.3 ± 1.1 l min−1; control: LLCT = 55.3 ± 10.9 s, Q = 4.5 ± 0.5 l min−1) to peak exercise (HF:LLCT = 20.6 ± 3.9* s, Q = 8.8 ± 2.5* l min−1; control:LLCT = 14.9 ± 2.4 s, Q = 16.5 ± 1.2 l min−1; *P < 0.05 vs control). LLCT was significantly (P < 0.05) slower for the HF group when compared to the control group during submaximal exercise and at peak exercise. However, at a fixed Q the HF subjects had a faster LLCT. We hypothesize that the faster LLCT at a fixed Q for HF patients, may be the result of a more intensive peripheral vasoconstriction of non-active beds and a better redistribution of blood flow.

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“…In fact, it was established that the normal lifespan of a human endothelial cell is approximately 30 years (Vanhoutte, 1996). In fact, it was established that the normal lifespan of a human endothelial cell is approximately 30 years (Vanhoutte, 1996).…”

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4-Hydroxynonenal induces dysfunction and apoptosis of cultured endothelial cells

et al. 1999

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Lipolytic products of triglyceride-rich lipoproteins, i.e., free fatty acids, may cause activation and dysfunction of the vascular endothelium. Mechanisms of these effects may include lipid peroxidation. One of the major and biologically active products of peroxidation of n-6 fatty acids, such as linoleic acid or arachidonic acid, is the aldehyde 4-hydroxynonenal (HNE). To study the hypothesis that HNE may be a critical factor in endothelial cell dysfunction caused by free fatty acids, human umbilical endothelial cells (HUVEC) were treated with up to160 microM of linoleic or arachidonic acid. HNE formation was detected by immunocytochemistry in cells treated for 24 h with either fatty acid, but more markedly with arachidonic acid. To study the cellulareffects of HNE, HUVEC were treated with different concentrations of this aldehyde, and several markers of endothelial cell dysfunction were determined. Exposure to HNE for 6 and 9 h resulted in increased cellular oxidative stress. However, short time treatment with HNE did not cause activation of nuclear factor-kappaB (NF-kappaB). In addition, HUVEC exposure to HNE caused a dose-dependent decrease in production of both interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1). On the other hand, HNE exerted prominent cytotoxic effects in cultured HUVEC, manifested by morphological changes, diminished cellular viability, and impaired endothelial barrier function. Furthermore, HNE treatment induced apoptosis of HUVEC. These data provide evidence that HNE does not contribute to NF-kappaB-related mechanisms of the inflammatory response in HUVEC, but rather to endothelial dysfunction, cytotoxicity, and apoptotic cell death.

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Endothelium‐dependent Responses and Inhibition of Angiotensin‐converting Enzyme

Cited by 10 publications

References 55 publications

Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure

Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure

Lung-to-lung circulation times during exercise in heart failure

4-Hydroxynonenal induces dysfunction and apoptosis of cultured endothelial cells

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