Angiotensin II formation by an alternative pathway during exercise in humans

Miura, Shin‐ichiro; Ideishi, Munehito; Sakai, Takaaki; Motoyama, Mitsugu; Kinoshita, Akio; Sasaguri, Manabu; Tanaka, Hiroaki; Shindo, Munehiro; Arakawa, Kikuo

doi:10.1097/00004872-199410000-00008

Cited by 47 publications

(40 citation statements)

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“…14 Another enzyme present in mast cells is the metalloprotease, carboxypeptidase A enzyme. This enzyme cleaves the His 9 -Leu 10 bond in angiotensin I and as a result generates the fragment angiotensin [1][2][3][4][5][6][7][8][9] , which although capable of inhibiting ACE, has no known intrinsic contractile activity. 26 The human heart has been shown to possess carboxypeptidase A activity, generation of angiotensin [1][2][3][4][5][6][7][8][9] by this enzyme is sufficient to block cardiac ACE.…”

Section: Alternative Angiotensin II Generating Enzymesmentioning

confidence: 99%

“…This enzyme cleaves the His 9 -Leu 10 bond in angiotensin I and as a result generates the fragment angiotensin [1][2][3][4][5][6][7][8][9] , which although capable of inhibiting ACE, has no known intrinsic contractile activity. 26 The human heart has been shown to possess carboxypeptidase A activity, generation of angiotensin [1][2][3][4][5][6][7][8][9] by this enzyme is sufficient to block cardiac ACE. 27 It is undetermined if human blood vessels also exhibit cardoxypeptidase A activity, or if endogenous local ACE activity in the vessel wall is regulated by the synthesis of angiotensin [1][2][3][4][5][6][7][8][9] .…”

Section: Alternative Angiotensin II Generating Enzymesmentioning

confidence: 99%

“…26 The human heart has been shown to possess carboxypeptidase A activity, generation of angiotensin [1][2][3][4][5][6][7][8][9] by this enzyme is sufficient to block cardiac ACE. 27 It is undetermined if human blood vessels also exhibit cardoxypeptidase A activity, or if endogenous local ACE activity in the vessel wall is regulated by the synthesis of angiotensin [1][2][3][4][5][6][7][8][9] . Other angiotensin fragments may be generated by the action of neutral endopeptidase 24.11 and propyl-endopeptidase 24.26.…”

Section: Alternative Angiotensin II Generating Enzymesmentioning

confidence: 99%

“…Exerciseinduced angiotensin II release in healthy volunteers can be inhibited by the serine protease inhibitor nafamostat. 8 This drug is also beneficial in patients with peripheral vascular disease. 7 It was originally thought that nafamostat could block the effect of chymase, however, it is now claimed that this inhibitor has no activity against chymase or ACE.…”

Section: Role Of Chymase In Diseasementioning

confidence: 99%

“…5,6 In addition, increases in plasma angiotensin II following exercise or during ischaemic conditions could not be prevented by an ACE inhibitor. 7,8 The concept of alternative pathways for angiotensin II formation is supported by a number of in vivo and in vitro experiments. For example, ACE inhibitors alone have been shown to be unable to completely block angiotensin II generation in the human heart and detrusor muscle or block the contractile effect of angiotensin I in isolated blood vessels.…”

Section: Introductionmentioning

confidence: 99%

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Chymase-dependent angiotensin II formation in human blood vessels

Chester

Jaa

2000

J Hum Hypertens

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Section: Alternative Angiotensin II Generating Enzymesmentioning

confidence: 99%

Section: Alternative Angiotensin II Generating Enzymesmentioning

confidence: 99%

Section: Alternative Angiotensin II Generating Enzymesmentioning

confidence: 99%

Section: Role Of Chymase In Diseasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chymase-dependent angiotensin II formation in human blood vessels

Chester

Jaa

2000

J Hum Hypertens

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Angiotensin II receptor antagonists in heart failure: Rationale and design of the evaluation of losartan in the elderly (ELITE) trial

Pitt

Chang²,

Timmermans³

1995

Cardiovasc Drug Ther

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Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective in reducing morbidity and mortality in patients with heart failure or post-myocardial infarction left ventricular dysfunction. Despite evidence from several large-scale randomized trials, the use of ACE-I in patients with heart failure remains relatively low. In part, the failure to achieve more widespread use of ACE-I in patients with heart failure may be due to physician's perceptions of the side effects associated with ACE-I, such as angioedema, renal dysfunction, cough, and hypotension. Many of these side effects are thought to be due to ACE-I-induced bradykinin accumulation. It is possible to inhibit the effect of angiotensin II without increasing bradykinin levels using an angiotensin II type I blocking agent such as losartan. How effective losartan is compared with an ACE-I is uncertain, however. Some of the beneficial effects of ACE-I have been attributed to bradykinin accumulation, and therefore ACE-I might have an advantage compared with an angiotensin II type I receptor antagonist such as losartan. On the other hand, angiotensin II may be produced by non-ACE-I-dependent mechanisms, which would suggest that an angiotensin II type I receptor blocking agent would be advantageous. To determine the relative safety and efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of angiotensin II, versus an angiotensin II type I receptor blocking agent, which does not result in bradykinin accumulation, we have begun the Evaluation of Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy of captopril and losartan in elderly patients with heart failure.

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The serum angiotensin-converting enzyme and angiotensin II response to altered posture and acute exercise, and the influence of ACE genotype

Woods

Sanders

Jones

et al. 2004

European Journal of Applied Physiology

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The deletion (D) rather than insertion (I) allele of the angiotensin-converting enzyme (ACE) gene is associated with greater ACE activity. We examined: (1) the influence of posture change (recumbent to seated) and acute exercise on serum ACE and angiotensin II (Ang II) activity; (2) the relationship between ACE and Ang II levels; and (3) the influence of ACE genotype on changes in ACE and Ang II levels with posture and exercise. Recreationally active young male Caucasians (10 each of II, ID and DD genotypes) rested for 35 min supine then 15 min upright, took 20 min bicycle ergometric exercise at 70% maximum oxygen uptake, then rested for 40 min. Samples were taken throughout for ACE activity and Ang II levels. Supine ACE levels were dependent upon ACE genotype [24.8 (5.7), 26.9 (4.5), 45.5 (6.4) nmol His-Leu ml(-1) min(-1); II, ID, DD, respectively; P<0.00005] and thereafter. ACE activity rose with assumption of a seated posture [from 32.4 (10.9) nmol His-Leu ml(-1) min(-1) to 35.0 (11.5) nmol His-Leu ml(-1) min(-1), P<0.00001], the absolute rise being independent of genotype [3.22 (1.92), 1.6 (1.6), 2.4 (2.3) nmol His-Leu ml(-1) min(-1); II, ID, DD; P=0.22], unlike percentage change [12.8 (6.8), 5.6 (5.5), 5.3 (5.0)%; II, ID, DD; P<0.01, and P=0.004 for II vs presence of the D allele]. A further genotype-independent rise occurred with exercise [+2.9 (3.7) units, P<0.0003]. An associated rise in Ang II levels [30.3 (15.9), or 2587.9 (489.76)%, P<0.00001] was independent of ACE genotype or activity. Upright posture increases ACE activity, and this may be influenced by ACE genotype. ACE activity and Ang II levels rise independently with exercise in a non-genotype-dependent fashion.

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Angiotensin II formation by an alternative pathway during exercise in humans

Cited by 47 publications

References 0 publications

Chymase-dependent angiotensin II formation in human blood vessels

Chymase-dependent angiotensin II formation in human blood vessels

Angiotensin II receptor antagonists in heart failure: Rationale and design of the evaluation of losartan in the elderly (ELITE) trial

The serum angiotensin-converting enzyme and angiotensin II response to altered posture and acute exercise, and the influence of ACE genotype

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