Abstract:
:Nitroglycerin dilates large (greater than or equal to 100 microns) but not small coronary arterial microvessels, and a putative metabolite of nitroglycerin, S-nitroso-L-cysteine, has been shown in vitro to dilate both large and small coronary microvessels. Based on this evidence, we tested the hypothesis that the lack of response of small coronary microvessels was due to an inability of small coronary microvessels to convert nitroglycerin into its vasoactive metabolite and examined possible explanations for this phenomenon. We studied left ventricular epicardial microvessels in vivo using video microscopy and stroboscopic epi-illumination in anesthetized, open-chest dogs. Diameters were determined while the epicardium was suffused with nitroglycerin, S-nitroso-L-cysteine, or S-nitroso-D-cysteine (all 10 microM) and nitroglycerin in the presence of L- or D-cysteine (100 microM). None of the agents affected systemic hemodynamics. Nitroglycerin dilated large arterioles (20 +/- 2%) but not small arterioles (1 +/- 1%). Both S-nitroso-L-cysteine and S-nitroso-D-cysteine were potent dilators of all size classes of microvessels. Concomitant application of L-cysteine and nitroglycerin evoked dilation in small microvessels (22 +/- 4%, p less than 0.5 versus nitroglycerin alone) and larger microvessels (27 +/- 6%, p = NS versus nitroglycerin alone). D-Cysteine did not alter the microvascular response to nitroglycerin in either small (7 +/- 4%, p = NS versus nitroglycerin alone) or large (18 +/- 3%, p = NS versus nitroglycerin alone) microvessels. Neither L-cysteine nor D-cysteine had a direct effect on microvascular diameter. These findings suggest that 1) sulfhydryl groups are required for the conversion of nitroglycerin to its vasoactive metabolite; 2) the interaction between nitroglycerin and sulfhydryl residues is a stereospecific process, indicating either an intracellular mechanism or a membrane-associated enzymatic reaction; and 3) a lack of available sulfhydryl groups may be responsible for the lack of response of small coronary arterioles to nitroglycerin.
journal_name
Circ Resjournal_title
Circulation researchauthors
Kurz MA,Lamping KG,Bates JN,Eastham CL,Marcus ML,Harrison DGdoi
10.1161/01.res.68.3.847subject
Has Abstractpub_date
1991-03-01 00:00:00pages
847-55issue
3eissn
0009-7330issn
1524-4571journal_volume
68pub_type
杂志文章abstract:RATIONALE:Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Previous studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation....
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.310283
更新日期:2017-06-09 00:00:00
abstract::Although morphological studies suggest that coronary vascular injury is a result of prolonged ischemia and subsequent reperfusion, whether functional coronary microvascular injury develops during brief in vivo ischemia is unclear. In other organs, permeability is a sensitive indicator of functional vascular injury. Th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.4.986
更新日期:1990-04-01 00:00:00
abstract::Mitochondria have long been known to play a critical role in maintaining the bioenergetic status of cells under physiological conditions. It was also recognized early in mitochondrial research that the reduction of oxygen to generate the free radical superoxide occurs at various sites in the respiratory chain and was ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000248212.86638.e9
更新日期:2006-10-27 00:00:00
abstract::Beta(1)- and beta(2)-adrenergic receptors (betaARs) are known to differentially regulate cardiomyocyte contraction and growth. We tested the hypothesis that these differences are attributable to spatial compartmentation of the second messenger cAMP. Using a fluorescent resonance energy transfer (FRET)-based approach, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000250046.69918.d5
更新日期:2006-11-10 00:00:00
abstract::Activity was recorded from physiologically identified baroreceptor or chemoreceptor fibers in carotid sinus nerves of urethane-anesthetized spontaneously breathing rabbits. A carotid sinus area was vascularly isolated so that carotid sinus pressure and perfusion medium (Locke's solution or rabbit blood) could be contr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.6.1608
更新日期:1991-12-01 00:00:00
abstract::cAMP-dependent protein kinase is anchored to discrete cellular compartments by a family of proteins, the A-kinase anchor proteins (AKAPs). We have investigated in vivo and in vitro the biological effects of the expression of a prototypic member of the family, AKAP75, on smooth muscle cells. In vitro expression of AKAP...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.3.319
更新日期:2001-02-16 00:00:00
abstract::Mitogen-activated protein kinase kinase (MKK)4 is a critical member of the mitogen-activated protein kinase family. It is able to activate the c-Jun NH(2)-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase in response to environmental stresses. JNK and p38 are strongly implicated in pathological ca...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.188292
更新日期:2009-04-10 00:00:00
abstract::Inherited restrictive cardiomyopathy (RCM) is a debilitating disease characterized by a stiff heart with impaired ventricular relaxation. Mutations in cardiac troponin I (cTnI) were identified as causal for RCM. Acute genetic engineering of adult cardiac myocytes was used to identify primary structure/function effects...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000268412.34364.50
更新日期:2007-05-25 00:00:00
abstract::In urethane-anesthetized rats, electrophysiological recordings of spontaneously active neurons in the vasopressor area of the rostral ventrolateral medulla were analyzed for participation in cardiovascular regulation. A total of 138 units were found which were inhibited by transient increases in mean arterial pressure...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.3.359
更新日期:1985-03-01 00:00:00
abstract::Nitric oxide (NO) exerts important vasodilatory, antiplatelet, antioxidant, antiadhesive, and antiproliferative effects. Although endothelium derived NO has been shown to be of prime importance in cardio- and vasculoprotection, until recently little was known about the role of platelet-derived NO. New evidence suggest...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.107.158410
更新日期:2007-09-28 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1301.092508
更新日期:2001-07-06 00:00:00
abstract::The effect of chronic therapy with quinapril on the temporal progression of left ventricular failure and survival was assessed in the CHF 146 cardiomyopathic (CM) hamster, which is an idiopathic model of congestive heart failure. Age-matched Golden Syrian (GS) hamsters served as normal controls. Quinapril was administ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.5.1302
更新日期:1991-05-01 00:00:00
abstract::A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.6.759
更新日期:1979-06-01 00:00:00
abstract::The alpha-adrenergic blocking drugs, phentolamine and Hydergine, both act centrally at different sites to depress and enhance the pressor and sympathetic nerve response to decreased baroreceptor afferent input in anesthetized cats. Depression of the rise in blood pressure and sympathetic nerve discharge during bilater...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.5.724
更新日期:1976-11-01 00:00:00
abstract::Nitric oxide (NO) functions principally as a diffusible paracrine effector. The exception is in cardiomyocytes where both NO synthases (NOS) and target proteins coexist, allowing NO to work in an autocrine/intracrine fashion. However, the most abundant myocyte isoform (NOS3) is far more expressed in vascular endotheli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000119323.79644.20
更新日期:2004-03-19 00:00:00
abstract::The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosis. Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an att...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.182535
更新日期:2009-01-30 00:00:00
abstract::Although urinary sodium excretion is positively influenced by acute changes in renal perfusion pressure, micropuncture studies show highly conflicting results concerning the response of superficial proximal tubule sodium reabsorption to changes in renal perfusion pressure. In the present study, the changes of superfic...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1184
更新日期:1990-05-01 00:00:00
abstract::Isolated, cultured arterial endothelial cells express an acetylcholine (ACh)-activated K+ current in addition to an inward rectifier current whose conductance is unaffected by ACh. The cholinergic K+ current is specifically blocked by atropine (1 microM) and shows single saturation kinetics with ACh (half-maximal stim...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.6.1059
更新日期:1988-06-01 00:00:00
abstract::The aim was to identify energy-consuming processes, other than contraction, downregulated during moderate hypoxia ( approximately 5 micromol/L, 0.5% O(2)) and severe hypoxia (<0.5 micromol/L, <0.05% O(2)) in isolated neonatal cardiomyocytes. The metabolic response of cardiomyocytes to moderate and severe hypoxia was a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000015592.95986.03
更新日期:2002-04-19 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.4.906
更新日期:1992-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2004-08-06 00:00:00
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更新日期:2011-12-09 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.1.300
更新日期:1991-01-01 00:00:00
abstract:RATIONALE:Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. OBJECTIVE:In this article, we outline the basis for a possible link ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.308763
更新日期:2016-06-24 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000262653.84850.8b
更新日期:2007-04-13 00:00:00
abstract::Three different isoforms of the inhibitory guanine nucleotide-binding protein alpha-subunit (Gi alpha) have been cloned. However, little information on the cardiac-specific expression of these isoforms is available. The deduced amino acid sequence of a full-length Gi alpha 2 complementary DNA from a canine ventricular...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.4.1136
更新日期:1989-10-01 00:00:00
abstract:RATIONALE:We have recently shown that the bone morphogenetic protein (BMP) antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. Our initial studies discovered that Grem2 is strongly induced in the adult heart after experimental myocardial infarction (MI). However, th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308700
更新日期:2016-07-22 00:00:00
abstract:RATIONALE:Pulmonary arterial hypertension (PAH) remains a progressive and eventually lethal disease characterized by increased pulmonary vascular resistance because of loss of functional lung microvasculature, primarily at the distal (intracinar) arteriolar level. Cell-based therapies offer the potential to repair and ...
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pub_type: 杂志文章,多中心研究
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更新日期:2015-09-11 00:00:00
abstract::In our morphometric study of the effects of exercise on the heart, male Wistar-Kyoto rats at 5 weeks of age were subjected daily to a moderate treadmill running program that lasted for 7 weeks. The heart responded to physical conditioning by different magnitudes of tissue growth of the right (22%) and left (7%) ventri...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.1.57
更新日期:1983-01-01 00:00:00
abstract::Transformer splicing regulatory proteins determine the sexually dimorphic traits of Drosophila. The role of the vertebrate homologs of Tra-2 in phenotypic specification is undefined. We are using the alternative splicing of the MYPT1 E23 exon as a model for the study of smooth muscle diversification into fast and slow...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2008-08-29 00:00:00