Abstract:
:We determined whether local bradykinin production modulates cardiac adrenergic activity. Depolarization of guinea pig heart sympathetic nerve endings (synaptosomes) with 1 to 100 mmol/L K+ caused the release of endogenous norepinephrine (10% to 50% above basal level). This release was exocytotic, because it depended on extracellular Ca2+, was inhibited by the N-type Ca(2+)-channel blocker omega-conotoxin and the protein kinase C inhibitor Ro31-8220, and was potentiated by the neuronal uptake-1 inhibitor desipramine. Typical of adrenergic terminals, norepinephrine exocytosis was enhanced by activation of prejunctional angiotensin AT1-receptors and attenuated by adrenergic alpha 2-receptors, adenosine A1-receptors, and histamine H3-receptors. Exogenous bradykinin enhanced norepinephrine exocytosis by 7% to 35% (EC50, 17 nmol/L), without inhibiting uptake 1. B2-receptor, but not B1-receptor, blockade antagonized this effect. The kininase II/angiotensin-converting enzyme inhibitor enalaprilat and the addition of kininogen or kallikrein enhanced norepinephrine exocytosis by approximately equal to 6% to 40% (EC50, 20 nmol/L) and approximately equal to 25% to 60%, respectively. This potentiation was prevented by serine protease inhibitors and was antagonized by B2-receptor blockade. Therefore, norepinephrine exocytosis is augmented when bradykinin synthesis is increased or when its breakdown is inhibited. This is the first report of a local kallikrein-kinin system in adrenergic nerve endings capable of generating enough bradykinin to activate B2-receptors in an autocrine/paracrine fashion and thus enhance norepinephrine exocytosis. This amplification process may operate in disease states, such as myocardial ischemia, associated with severalfold increases in local kinin concentrations.
journal_name
Circ Resjournal_title
Circulation researchauthors
Seyedi N,Win T,Lander HM,Levi Rdoi
10.1161/01.res.81.5.774subject
Has Abstractpub_date
1997-11-01 00:00:00pages
774-84issue
5eissn
0009-7330issn
1524-4571journal_volume
81pub_type
杂志文章abstract::Controversy exists regarding the mechanism by which catecholamines stimulate renin secretion in vivo. A sensitive rat kidney slice system was utilized to study the direct effects of adrenergic agonists and antagonists on renin release in vitro. Catecholamines were protected from degradation by the addition of ascorbic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.3.318
更新日期:1975-09-01 00:00:00
abstract::Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal growth. We showed previously that TGF-beta(1) stimulates intimal growth through early upregulation of plasminogen activator inhibitor-1 (PAI-1) and, subsequently, PAI-1-dependent increases in cell migration and matrix accumulation. We also show...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000266970.34017.8d
更新日期:2007-05-11 00:00:00
abstract:RATIONALE:ATP-binding cassette transporter A1 (ABCA1) plays a critical role in eliminating excess free cholesterol from tissues by effluxing cellular free cholesterol and phospholipids to lipid-poor apolipoprotein AI. Macrophage ABCA1 also dampens proinflammatory myeloid differentiation primary-response protein 88-depe...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.269043
更新日期:2012-11-09 00:00:00
abstract::Cellular mechanisms underlying beta-adrenergic stimulation of the arrhythmogenic transient inward current (TI) were investigated by using a two-microelectrode voltage-clamp technique in rabbit cardiac Purkinje fibers. TI induced by elevating [Ca2+]o to 30 mmol/L and substituting [Na+]o with N-methyl-D-glucamine (NMG) ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.4.664
更新日期:1995-04-01 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...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.58
更新日期:1975-01-01 00:00:00
abstract::In response to hypoxia and reoxygenation, mammalian cells are known to express a variety of genes to adapt to these external stresses or lead to further cell damage. We investigated the intracellular signaling cascades in cultured rat cardiac myocytes subjected to hypoxia followed by reoxygenation (hypoxia/reoxygenati...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.1.82
更新日期:1996-01-01 00:00:00
abstract::In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.1.101
更新日期:1975-07-01 00:00:00
abstract::In the early (3-day) stage of development, long-lasting openings of the L-type Ca2+ channels (mode 2) occur in embryonic chick heart cells. Since mode-2 behavior is infrequently observed in adult heart cells of other species, in the present study, developmental change in behavior of the Ca2+ channel was examined in yo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.376
更新日期:1992-08-01 00:00:00
abstract::Basic calcium phosphate (BCP) crystal deposition underlies the development of arterial calcification. Inflammatory macrophages colocalize with BCP deposits in developing atherosclerotic lesions and in vitro can promote calcification through the release of TNF alpha. Here we have investigated whether BCP crystals can e...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000171451.88616.c2
更新日期:2005-06-24 00:00:00
abstract::Red blood cells and lysate products (erythrolysate) are observed consistently in lymph draining acute and chronic inflammatory reactions and from tissues subjected to trauma or surgical procedures. Using hemoglobin as a marker for erythrolysate, we have measured hemoglobin in lymph up to the 10(-6) M range in a number...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.5.1097
更新日期:1990-11-01 00:00:00
abstract::Obesity results in marked alterations in cardiac energy metabolism, with a prominent effect being an increase in fatty acid uptake and oxidation by the heart. Obesity also results in dramatic changes in the release of adipokines, such as leptin and adiponectin, both of which have emerged as important regulators of car...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.107.150417
更新日期:2007-08-17 00:00:00
abstract::Congenital heart disease (CHD) is the most common congenital anomaly in newborn babies. Cardiac malformations have been produced in multiple experimental animal models, by perturbing selected molecules that function in the developmental pathways involved in myocyte specification, differentiation, or cardiac morphogene...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.112.300853
更新日期:2013-02-15 00:00:00
abstract::We created knock-in mice in which a deletion of 3 base pairs coding for K210 in cardiac troponin (cTn)T found in familial dilated cardiomyopathy patients was introduced into endogenous genes. Membrane-permeabilized cardiac muscle fibers from mutant mice showed significantly lower Ca(2+) sensitivity in force generation...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.106.146670
更新日期:2007-07-20 00:00:00
abstract::Fractalkine, a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1, and the CX3CR1 polymorphism V249I affects receptor expression and function. Here we show that this polymorphism is an independent risk factor for atherosclerotic coronary artery disease (CAD). ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1701.095642
更新日期:2001-08-31 00:00:00
abstract::Five fetal sheep (gestational age, 118 to 125 days) were instrumented to measure impedances of the lower abdominal aorta. Four days after surgery, flow and pressure pulses were recorded during control conditions and during infusion of norepinephrine (0.3 to 3 micrograms.min-1.kg-1 body weight) or angiotensin II (0.2 t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.4.641
更新日期:1994-04-01 00:00:00
abstract::Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Incre...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.109.197996
更新日期:2009-06-05 00:00:00
abstract::We studied a Syrian family with 3 children who had low-density lipoprotein cholesterol (LDL) concentrations of 13.3, 12.2, and 8.6 mmol/L, respectively. Three other siblings and the parents all had LDL values <4.52 mmol/L, suggesting an autosomal-recessive mode of inheritance. The extended pedigree had 66 additional p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000018002.43041.08
更新日期:2002-05-17 00:00:00
abstract::The purpose of this study was to evaluate the limitations of the double sucrose gap voltage clamp technique in the determination of tension-voltage relationships for frog atrial muscle. Tension-voltage relationships were determined under two conditions. In one case we determined both the tension response and slow inwa...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.1.106
更新日期:1976-07-01 00:00:00
abstract::We have previously shown that a cryoactivatable inactive form of renin, which we have tentatively termed prorenin, occurs in human plasma. Plasma prorenin is measured by subtracting the endogenous plasma renin activity (PRA) from the total renin activity measured after cryoactivation. Cryoactivation is accomplished by...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract:RATIONALE:Clinical studies have shown that Sirt3 (Sirtuin 3) expression declines by 40% by 65 years of age paralleling the increased incidence of hypertension and metabolic conditions further inactivate Sirt3 because of increased NADH (nicotinamide adenine dinucleotide, reduced form) and acetyl-CoA levels. Sirt3 impair...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.310933
更新日期:2017-08-18 00:00:00
abstract::Although clinical studies suggest that chronic hypercapnic acidosis may be associated with renal sodium retention, little information is available on the effect of acute hypercapnic acidosis on renal sodium excretion. We, therefore, increased PCO2 from 23 to 74 mm Hg in anesthetized dogs and observed a marked antinatr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.50.2.294
更新日期:1982-02-01 00:00:00
abstract::Changes in cardiac filling pressure (central venous pressure) were measured following carotid occlusion and infusions of catecholamines in awake dogs while cardiac output was held constant. After carotid occlusion in dogs with vagi blocked, central venous pressure increased about 0.8 mm Hg (an estimated decrease in va...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.4.440
更新日期:1984-10-01 00:00:00
abstract::Two characteristic features of the rapid component of the cardiac delayed rectifier current (IKr) are prominent inward rectification and an unexpected reduction in activating current with decreased [K+]o. Similar features are observed with heterologous expression of HERG, the gene thought to encode the channel carryin...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.6.782
更新日期:1997-06-01 00:00:00
abstract::Several time- and voltage-dependent ionic currents have been identified in cardiac pacemaker cells, including Na(+) current, L- and T-type Ca(2+) currents, hyperpolarization-activated cation current, and various types of delayed rectifier K(+) currents. Mathematical models have demonstrated that spontaneous action pot...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.87.2.88
更新日期:2000-07-21 00:00:00
abstract::Electrical responses induced by perivasascular nerve stimulation were recorded intracellularly from the smooth muscle of dog middle cerebral artery. With nerve stimulation, the muscle membrane produced excitatory junction potential and then a slow hyperpolarization. The excitatory junction potential showed facilitatio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.51.6.751
更新日期:1982-12-01 00:00:00
abstract::Current management of ventricular septal defect (VSD) after myocardial infarction (MI) is aimed at improving left ventricular (LV) performance by afterload reduction as a means of hemodynamic stabilization or shunt control. The current investigation was undertaken to determine whether primary manipulation of right ven...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.4.372
更新日期:1977-04-01 00:00:00
abstract:RATIONALE:Remote ischemic preconditioning (rIPC) with short episodes of ischemia/reperfusion (I/R) of an organ remote from the heart is a powerful approach to protect against myocardial I/R injury. The signal transduction pathways for the cross talk between the remote site and the heart remain unclear in detail. OBJEC...
journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCRESAHA.114.303822
更新日期:2014-05-09 00:00:00
abstract::Postnatal development of the mammalian heart is associated with changes in the population of isoforms of the thin filament proteins. We correlated the change in thin filament proteins, which occur in rabbit hearts between 5 days and 22 days of age, with changes in Ca2+ dependence of myofibrillar ATPase activity, force...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1204
更新日期:1990-05-01 00:00:00
abstract::One of the major manifestations of obesity is increased production of the adipocyte-derived 16-kDa peptide leptin, which is also elevated in heart disease, including congestive heart failure. However, whether leptin can directly alter the cardiac phenotype is not known. We therefore studied the effect of leptin as a p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000089255.37804.72
更新日期:2003-08-22 00:00:00
abstract::Studies were carried out to determine the contribution of cardiopulmonary receptors to the renal responses to head-out water immersion in the nonhuman primate. Immersion to the suprasternal notch was associated with significant increases in central venous pressure, urine flow, and sodium excretion. The increased sodiu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.42.2.263
更新日期:1978-02-01 00:00:00