Abstract:
:Local inhibition of angiotensin-converting enzyme (ACE, kininase II) produces both attenuation of angiotensin (Ang) II generation and bradykinin (BK) degradation. To delineate the participation of BK in the cardioprotective actions of ACE inhibitors, experiments were performed in rats and dogs with cardiac ischemia-reperfusion injuries. (I) In rat isolated perfused working hearts with regional myocardial ischemia, BK in concentrations as low as 1 X 10(-9) M increased coronary flow (CF) and reduced the incidence and duration of reperfusion ventricular fibrillation (VF). In addition, enzyme activities of lactate dehydrogenase (LDH) and creatine kinase as well as lactate output were decreased in the venous effluent of BK-perfused hearts, which also showed improved cardiodynamic and metabolic parameters. Even concentrations of BK lower than 1 X 10(-10) M, which were without influence on coronary flow, exerted comparable beneficial metabolic effects connected with reduced incidence and duration of VF. Combined perfusions with threshold concentrations of BK (1 X 10(-12) M) and the ACE inhibitor ramiprilat (2.58 X 10(-9) M), which were ineffective given alone, resulted in a marked cardioprotective effect. Perfusion with Ang II (1 X 10(-9) M) aggravated reperfusion arrhythmias and worsened myocardial metabolism. BK perfusion prevented this deterioration in a concentration-dependent manner, whereas the Ang II receptor antagonist saralasin was only marginally effective. The BK antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]-BK (1 X 10(-5) M) completely abolished the cardioprotective effects of BK or the ACE inhibitor. However, higher concentrations of BK (1 X 10(-7) M) or ramiprilat (2.58 X 10(-5) M) competitively reversed these properties of the BK antagonist. (II) In anesthetized dogs, BK was infused into the coronary artery in a dose of 1 ng/kg/min during occlusion (90 min) and reperfusion (30 min) of the left descending coronary artery (LAD)--a dose without effects on cardiovascular parameters. In line with the findings in isolated ischemic rat hearts, BK infusion reduced LDH activities and lactate concentrations in the coronary sinus blood, whereas myocardial tissue levels of glycogen and energy-rich phosphates were increased in the infarcted area. The cardioprotective effects produced by perfusion with BK or by reduction of BK degradation through local interference with ACE favor a role for BK in ischemia-reperfusion injuries in rats and dogs.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Linz W,Martorana PA,Schölkens BAsubject
Has Abstractpub_date
1990-01-01 00:00:00pages
S99-109eissn
0160-2446issn
1533-4023journal_volume
15 Suppl 6pub_type
杂志文章abstract::Oxygen-derived free radicals and their metabolites may contribute to the extension of irreversible cellular injury, which occurs on reperfusion of the previously ischemic myocardium. Therefore, therapy directed against the toxic effects of reactive oxygen species may provide protection to the ischemic myocardium, whic...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::Nitrates are beneficial in post-myocardial infarction patients with stable, unstable, and Prinzmetal's variant angina and as adjunctive therapy in congestive heart failure. They are available in multiple formulations that differ in chemical structure, pharmacokinetics, onset and duration of activity, and peak effect; ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1989-01-01 00:00:00
abstract::Since minoxidil was previously shown to raise plasma renin activity (PRA) but not the plasma aldosterone concentration (PAC), the effect of minoxidil on the rate of aldosterone metabolic clearance was studied. After the addition of minoxidil to the antihypertensive regimen of 7 hypertensive patients, the aldosterone m...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198000022-00018
更新日期:1980-01-01 00:00:00
abstract::The pharmacologic properties of a novel nonpeptide endothelin (ET) receptor antagonist, S-1255 ([R]-[+]-2-[benzo(1,3)dioxol-5-yl]-6-isopropyl-4-[4-methoxyphenyl]-2H-chromene-3-carboxylic acid), was studied. [3H]S-1255 specifically bound to porcine aortic smooth muscle membranes expressing only ET(A) receptors with a K...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200104000-00014
更新日期:2001-04-01 00:00:00
abstract::Addition of endothelin-1 (ET-1) to primary cultures of bovine adrenal chromaffin cells causes a significant enhancement of norepinephrine and epinephrine efflux, with an EC50 of about 1 nM. A maximally effective concentration of endothelin (10 nM) gives a transient increase in noradrenaline release within 5 min. The a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198900135-00066
更新日期:1989-01-01 00:00:00
abstract::Anakinra is a recombinant human interleukin 1 receptor antagonist that competes and blocks the biologic effects of interleukin 1, reducing systemic inflammatory responses. In the 2015 guidelines for the diagnosis and management of pericardial diseases of the European Society of Cardiology, anakinra was established as ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000839
更新日期:2020-07-01 00:00:00
abstract::Peripheral vascular resistance, arterial blood pressure, and left ventricular hypertrophy (LVH) are closely related. In systemic hypertension, hemodynamic changes in systolic and diastolic function accompany LVH. Both of these cardiac functions are detected with echocardiography and were measured during this study in ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Adenosine A1 receptor (A1AR) activation contracts smooth muscle, although signaling mechanisms are not thoroughly understood. Activation of A1AR leads to metabolism of arachidonic acid, including the production of 20-hydroxyeicosatetraenoic acid (20-HETE) by cytochrome P4504a (CYP4a). The 20-HETE can activate protein ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3182919591
更新日期:2013-07-01 00:00:00
abstract::The distribution of 3H-digoxin has been measured in a large number of tissues from the central, autonomic, and peripheral nervous system after the induction of ventricular tachycardia by infusing digoxin into anesthetized dogs. In most parts of the nervous system the tissue digoxin concentration was close to that in t...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198111000-00017
更新日期:1981-11-01 00:00:00
abstract::We compared left ventricular (LV) hemodynamics, LV muscle mass (LVMM), and LV geometry of 13 spontaneously hypertensive rats (SHRs) treated for 20 weeks with nifedipine (30 mg/kg/day) with those of 11 age-matched untreated SHRs. LVMM, LVMM related to end-diastolic volume (LVMM/EDV), LV pressure (PLV), systolic wall st...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198301000-00008
更新日期:1983-01-01 00:00:00
abstract::As a receptor for transforming growth factor-β, nodal and activin, activin receptor-like kinase 7 (ALK7) previously acts as a suppressor of tumorigenesis and metastasis, which has emerged to play a key role in cardiovascular diseases. However, the potential effect and molecular mechanism of ALK7 on vascular smooth mus...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000857
更新日期:2020-08-01 00:00:00
abstract::We investigated whether resveratrol (RSV) can attenuate obesity and diabetes progression and improve diabetes-induced vascular dysfunction, and we attempted to delineate its underlying mechanisms. Male C57Bl/6 mice were administered a high-fat diet (HFD) for 17 weeks. Mice developed type 2 diabetes with increased body...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000621
更新日期:2018-11-01 00:00:00
abstract::On the basis of animal studies, it has been proposed that calcium antagonists selectively interfere with the pressor response to alpha 2-adrenoceptor antagonists and have less direct action on alpha 1-adrenoceptor mechanisms. In placebo-controlled randomized studies in healthy normotensives, we have found that verapam...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198500076-00036
更新日期:1985-01-01 00:00:00
abstract::The relation between insulin resistance/ hyperinsulinemia and cardiovascular disease may be related to one of the cardiovascular effects of insulin. In acute experiments in humans, systemic euglycemic hyperinsulinemia induced vasodilation in skeletal muscle. Furthermore, the sympathetic nervous system is activated, al...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00005344-199608000-00010
更新日期:1996-08-01 00:00:00
abstract::To investigate the electrophysiological effects of propranolol in vivo over a wide range of plasma concentrations and to distinguish effects due to beta-blockade from those due to a direct membrane action, His bundle electrograms were recorded, and ventricular effective refractory periods (VERP) and monophasic action ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198107000-00004
更新日期:1981-07-01 00:00:00
abstract::The effects of tilisolol, a nonselective beta-adrenoceptor blocker, on transmembrane ionic currents were studied in single guinea pig ventricular myocytes by using the whole-cell voltage clamp technique. In the absence of beta-adrenergic stimulation, 10 microM tilisolol, a concentration higher than that used in the cl...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199705000-00005
更新日期:1997-05-01 00:00:00
abstract::Development of tolerance to nicorandil (NCR), N-(2-hydroxyethyl)nicotinamide nitrate (ester), was compared with that to nitroglycerin (NTG) or isosorbide dinitrate (ISDN) in dogs. An intracoronary arterial (i.a.) injection of NCR (20 micrograms), ISDN (30 micrograms), or NTG (1 microgram) caused coronary vasodilation....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::LY53857, spiperone, ketanserin, and setoperone were potent and competitive 5-HT2-receptor antagonists in the rat jugular vein with equivalent affinities at 5-HT2 receptors. In the rat jugular vein, ritanserin blocked 5-HT2-mediated contractile responses with a depression of the maximum response in concentrations great...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::A significant reduction of maximal vasodilation capacity at the calf in relation to the severity of the hypertensive state has been demonstrated in essential hypertension. The aim of this study was to evaluate the behavior of calf blood flow and vascular resistance in borderline hypertensives (BH) in comparison with n...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198608005-00025
更新日期:1986-01-01 00:00:00
abstract::The long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA) is severely limited by the high incidence of vascular restenosis. Endothelin-1 (ET-1) has been implicated in the pathogenesis of this response, since circulating levels of this potent smooth-muscle mitogen are elevated after PTCA. Therefor...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199322008-00097
更新日期:1993-01-01 00:00:00
abstract::The target proteins for calcium, when it acts as a second messenger, are a group of intracellular, specific calcium-binding proteins that contain EF-hand structures. Calmodulin regulates a number of Ca2+-dependent processes and is present in all eukaryotic cells. Parvalbumin, the S-100 proteins, two vitamin D-dependen...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1986-01-01 00:00:00
abstract::Effects of diltiazem on coronary vascular functional integrity were assessed in isolated rabbit hearts during reperfusion after 30 min of global, no-flow ischemia. External detection of radiolabeled albumin, [125I]bovine serum albumin ([125I]BSA), and compartmental-model analysis were used to estimate the mean transit...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198505000-00003
更新日期:1985-05-01 00:00:00
abstract::Endothelin-1 (ET-1) not only causes potent vasoconstriction but also leads to fluid retention, both actions mediated by ET(A)- and/or ET(B)-receptors. Selective ET(A)- and combined ET(A)/ET(B)-receptor antagonists improve hemodynamics in heart failure; however, it is also important to evaluate the effects of these ant...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200036051-00044
更新日期:2000-11-01 00:00:00
abstract::The positive inotropic effect of DPI 201-106 has been studied in isolated, electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WK). The positive inotropic effect of isoprenaline (Iso) and Ca2+ was studied for comparison. The maximal positive inotropic effect of Iso was...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198804000-00012
更新日期:1988-04-01 00:00:00
abstract::The purpose of this study was to assess the cardiovascular effects of an ultra-short-acting beta-blocker, ONO-1101, by using halothane-anesthetized beagle dogs in comparison with esmolol. ONO-1101 (n = 6) or esmolol (n = 6) was administered at four infusion rates of 0.3, 3, 30, and 300 microg/ kg/min. Each infusion wa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199907000-00012
更新日期:1999-07-01 00:00:00
abstract::Heart failure is associated with attenuation of parasympathetic nervous function and enhanced renin-angiotensin activity. We tested whether there was a dysfunction in the efferent cholinergic neurotransmission in the heart of rats with chronic myocardial infarction (MI) and the potential role of angiotensin II (Ang II...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199806000-00019
更新日期:1998-06-01 00:00:00
abstract::Allopurinol reduces formation of cytotoxic free radicals during myocardial ischemia/reperfusion in animals. To evaluate the effect of allopurinol on cardiac performance and metabolism after coronary bypass in humans, we divided 33 patients into two groups: 15 patients (controls) received no allopurinol and 18 patients...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-199501000-00019
更新日期:1995-01-01 00:00:00
abstract::A single dose of doxazosin, a long-acting postsynaptic alpha 1-adrenoceptor antagonist, was administered to seven patients with essential hypertension. Following administration of a single dose, all the patients except one who was forced to be discharged from the hospital for work, continuously received doxazosin once...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198707000-00013
更新日期:1987-07-01 00:00:00
abstract::Apoptosis of vascular cells is observed in vivo in normal vessel development and a variety of vascular pathologies. Apoptosis occurs in all cell types within the vessel wall, the consequences of which depend on both cell type and the pathology under study. The death receptor Fas is expressed throughout the vessel wall...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0b013e318198fe60
更新日期:2009-02-01 00:00:00
abstract::The vascular endothelium has a number of functions that may mediate many of the ischemia-reperfusion (IR) phenomena. The gatekeeper function is disturbed and increased capillary permeability results in edema and organ dysfunction. Vasomotor function is altered, with impairment of relaxation and augmentation of constri...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199600001-00007
更新日期:1996-01-01 00:00:00