Abstract:
:To elucidate the local effects of renin in the coronary circulation, we examined local angiotensin (Ang) I and II formation, as well as coronary vasoconstriction in response to renin administration, and compared the effects with exogenous infused Ang I. We perfused isolated hearts from rats overexpressing the human angiotensinogen gene in a Langendorff preparation and measured the hemodynamic effects and the released products. We also investigated cardiac Ang I conversion, including the contribution of non-angiotensin-converting enzyme-dependent Ang II-generating pathways. Finally, we studied Ang I conversion in vitro in heart homogenates. Renin and Ang I infusion both generated Ang II. Ang II release and vasoconstriction continued after renin infusion was stopped, even though renin disappeared immediately from the perfusate. In contrast, after Ang I infusion, Ang II release and coronary flow returned to basal levels. Ang I conversion (Ang II/Ang I ratio) was higher after renin infusion (0.109+/-0.027 versus 0.026+/-0.003, 15 minutes, P<.02) compared with infused Ang I. Remikiren added to the renin infusion abolished Ang I and II; captopril suppressed only Ang II, whereas an AT1 receptor blocker did not affect Ang I and II formation. All the drugs prevented renin-induced coronary flow changes. Total cardiac Ang II-forming activity was only partially inhibited by cilazaprilat (4.1+/-0.1 fmol x min(-1) x mg[-1]) and on a larger extent by chymostatin (2.6+/-0.3 fmol x min(-1) x mg[-1]) compared with control values (5.6+/-0.4 fmol x min(-1) x mg[-1]). We conclude that renin can be taken up by cardiac or coronary vascular tissue and induces long-lasting local Ang II generation and vasoconstriction. Locally formed Ang I was converted more effectively than infused Ang I. Furthermore, the comparison of in vivo and in vitro Ang I conversion suggests that in vitro assays may underestimate the functional contribution of angiotensin-converting enzyme to intracardiac Ang II formation.
journal_name
Circ Resjournal_title
Circulation researchauthors
Müller DN,Fischli W,Clozel JP,Hilgers KF,Bohlender J,Ménard J,Busjahn A,Ganten D,Luft FCdoi
10.1161/01.res.82.1.13subject
Has Abstractpub_date
1998-01-09 00:00:00pages
13-20issue
1eissn
0009-7330issn
1524-4571journal_volume
82pub_type
杂志文章abstract::Myocytes overlying a zone of infarction form the primary substrate for serious reentrant ventricular arrhythmias. In vitro and in vivo studies suggest that antiarrhythmic agents affect Na+ channels of cells from the epicardial border zone (EBZ) of the 5-day infarcted heart differently than they affect those of normal ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.4.431
更新日期:1998-08-24 00:00:00
abstract::The present study was undertaken to determine the mechanism of neointima formation in rabbit arteries subjected to extensive endothelial desquamation. Endothelial cells were selectively removed from the abdominal aorta by passing an inflated balloon catheter through the vessel. The healing response was then studied se...
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pub_type: 杂志文章
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abstract::Brugada syndrome has been linked to mutations in SCN5A. Agents that dissociate slowly from the sodium channel such as flecainide and ajmaline unmask the Brugada syndrome electrocardiogram and precipitate ventricular tachycardia/fibrillation. Lidocaine, an agent with rapid dissociation kinetics, has previously been sho...
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更新日期:2013-09-13 00:00:00
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更新日期:1988-10-01 00:00:00
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更新日期:1998-03-09 00:00:00
abstract:RATIONALE:Depletion of medial smooth muscle cell (SMC) is a major pathological characteristic of abdominal aortic aneurysm (AAA), although the mechanism by which these cells are eliminated remains incompletely understood. We reasoned that necroptosis, a recently described form of necrosis mediated by receptor-interacti...
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更新日期:2015-02-13 00:00:00
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更新日期:2016-12-09 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2014-01-17 00:00:00
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doi:10.1161/01.res.61.5.735
更新日期:1987-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.66.4.986
更新日期:1990-04-01 00:00:00
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更新日期:2005-08-19 00:00:00
abstract:RATIONALE:Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia and have a higher cardiovascular mortality than those without hyperhomocysteinemia by 10-fold. OBJECTIVE:We investigated monocyte differentiation in human CKD and cardiovascular disease (CVD). METHODS AND RESULTS:We identified CD40 as a...
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308750
更新日期:2016-11-11 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.86.3.286
更新日期:2000-02-18 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.84.5.587
更新日期:1999-03-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.1.185
更新日期:1990-01-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.6.1652
更新日期:1991-06-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2006-02-03 00:00:00
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更新日期:1983-08-01 00:00:00
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更新日期:2011-10-28 00:00:00
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更新日期:1986-08-01 00:00:00
abstract::Cardiovascular disease is a major killer in postmenopausal women in the industrialized societies. To investigate the effect of progestogen and 17 beta-estradiol replacement therapy on atherogenesis, we studied 60 cholesterol-fed ovariectomized rabbits for 13 weeks. They were randomly assigned to four groups of 15 rabb...
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pub_type: 杂志文章
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更新日期:1992-06-01 00:00:00
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更新日期:2004-07-23 00:00:00
abstract::The regeneration of new myocardium by stem or progenitor cells is an important therapeutic option. Cellular or nuclear fusion is considered as an alternative to cell reprogramming by transdifferentiation. However, the generation of hybrid cells may also be a consequence of a transient transmembrane exchange of protein...
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更新日期:2005-05-27 00:00:00
abstract:RATIONALE:The heart contains abundant interstitial and perivascular fibroblasts. Traditional views suggest that, under conditions of mechanical stress, cytokines, growth factors, and neurohumoral mediators stimulate fibroblast activation, inducing ECM (extracellular matrix) protein synthesis and promoting fibrosis and ...
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更新日期:2019-04-12 00:00:00
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更新日期:2013-10-25 00:00:00
abstract::Catecholamines and catecholamine-synthesizing enzymes have been examined in specific brain areas during the development of spontaneously (genetic) hypertensive (SH) rats. Changes in catecholamine metabolism were localized to regions of the brain implicated in the regulation of blood pressure. Norepinephrine levels and...
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pub_type: 杂志文章
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更新日期:1978-04-01 00:00:00
abstract::The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves substantial proteolysis of the arterial extracellular matrix. The lysosomal cysteine proteases can exert potent elastolytic and collagenolytic activity. Human atherosclerotic plaques have increased cysteine protease content and decreased levels...
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pub_type: 杂志文章
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更新日期:2005-02-18 00:00:00