摘要:

Abstract—Flow-induced dilation (FID) is dependent largely on hyperpolarization of vascular smooth muscle cells (VSMCs) in human coronary arterioles (HCA) from patients with coronary disease. Animal studies show that shear stress induces endothelial generation of hydrogen peroxide (H2O2), which is proposed as an endothelium-derived hyperpolarizing factor (EDHF). We tested the hypothesis that H2O2contributes to FID in HCA. Arterioles (135±7 &mgr;m, n=71) were dissected from human right atrial appendages at the time of cardiac surgery and cannulated with glass micropipettes. Changes in internal diameter and membrane potential of VSMCs to shear stress, H2O2, or to papaverine were recorded with videomicroscopy. In some vessels, endothelial H2O2generation to shear stress was monitored directly using confocal microscopy with 2′,7′-dichlorofluorescin diacetate (DCFH) or using electron microscopy with cerium chloride. Catalase inhibited FID (%max dilation; 66±8 versus 25±7%;P<0.05, n=6), whereas dilation to papaverine was unchanged. Shear stress immediately increased DCFH fluorescence in the endothelial cell layer, whereas treatment with catalase abolished the increase in fluorescence. Electron microscopy with cerium chloride revealed shear stress–induced increase in cerium deposition in intimal area surrounding endothelial cells. Exogenous H2O2dilated (%max dilation; 97±1%, ED50; 3.0±0.7×10−5mol/L) and hyperpolarized HCA. Dilation to H2O2was reduced by catalase, 40 mmol/L KCl, or charybdotoxin plus apamin, whereas endothelial denudation, deferoxamine, 1H-1,2,4-oxadiazole-[4,3-a]quinoxalin-1-one, or glibenclamide had no effect. These data provide evidence that shear stress induces endothelial release of H2O2and are consistent with the idea that H2O2is an EDHF that contributes to FID in HCA from patients with heart disease. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

When cardiac function and blood flow are first established are fundamental questions in mammalian embryogenesis. The earliest erythroblasts arise in yolk sac blood islands and subsequently enter the embryo proper to initiate circulation. Embryos staged 0 to 30 somites (S) were examined in utero with 40- to 50-MHz ultrasound biomicroscopy (UBM)-Doppler, to determine onset of embryonic heartbeat and blood flow and to characterize basic physiology of the very early mouse embryonic circulation. A heartbeat was first detected at 5 S, and blood vascular flow at 7 S. Heart rate, peak arterial velocity, and velocity-time integral showed progressive increases that indicated a dramatically increasing cardiac output from even the earliest stages. In situ hybridization revealed an onset of the heartbeat coincident with the appearance of yolk sac–derived erythroblasts in the embryo proper at 5 S. Early maturation of the circulation follows a tightly coordinated program.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Stimulation of &bgr;-adrenergic receptors (&bgr;ARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating &bgr;AR-stimulated apoptosis is not known. Stimulation of &bgr;ARs with norepinephrine (10 &mgr;mol/L) in the presence of prazosin (100 nmol/L) for 24 hours increased the number of apoptotic myocytes as determined by TUNEL staining by 3.6- fold. The superoxide dismutase/catalase mimetics Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 10 &mgr;mol/L) and Euk-134 decreased &bgr;AR-stimulated apoptosis by 89±6% and 76±10%, respectively. Infection with an adenovirus expressing catalase decreased &bgr;AR-stimulated apoptosis by 82±15%. The mitochondrial permeability transition pore inhibitor bongkrekic acid (50 &mgr;mol/L) decreased &bgr;AR-stimulated apoptosis by 76±8%, and the caspase inhibitor zVAD-fmk (25 &mgr;mol/L) decreased &bgr;AR-stimulated apoptosis by 62±11%. &bgr;AR-stimulated cytochromecrelease was inhibited by MnTMPyP. &bgr;AR stimulation caused c-Jun NH2-terminal kinase (JNK) activation, which was abolished by MnTMPyP. Transfection with an adenovirus expressing dominant-negative JNK inhibited &bgr;AR-stimulated apoptosis by 81±12%, and the JNK inhibitor SP600125 inhibited both &bgr;AR-stimulated apoptosis and cytochromecrelease. Thus, &bgr;AR-stimulated apoptosis in ARVMs involves ROS/JNK-dependent activation of the mitochondrial death pathway.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Abstract—The accepted paradigm considers the adult mammalian heart as a postmitotic organ, which possesses a relatively constant number of myocytes from shortly after birth to adulthood and senescence. This notion is questioned by the demonstration that although most adult myocytes are terminally differentiated, there is a small and continuously renewed subpopulation of cycling myocytes produced by the differentiation of cardiac stem-like cells. Myocyte death and myocyte regeneration are introduced as major determinants of cardiac homeostasis and alterations of ventricular anatomy and function in physiological and pathological states. The possibility of reconstituting dead myocardium by stem-like cells is advanced and proposed as a major area of future research.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Abstract—ATP-sensitive K+channels (KATP) contribute to vasomotor regulation in some species. It is not fully understood the extent to which KATPparticipate in regulating vasomotor tone under physiological and pathophysiological conditions in the human heart. Arterioles dissected from right atrial appendage were studied with video microscopy, membrane potential recordings, reverse transcription–polymerase chain reaction, and immunohistochemistry. Hypoxia produced endothelium-independent vasodilation and membrane hyperpolarization of vascular smooth muscle cells, both of which were attenuated by glibenclamide. Aprikalim, a selective KATPopener, also induced a potent endothelium-independent and glibenclamide-sensitive vasodilation with membrane hyperpolarization. Reverse transcription–polymerase chain reaction detected mRNA expression for KATPsubunits, and immunohistochemistry confirmed the localization of the inwardly rectifying Kir6.1 protein in the vasculature. In patients with type 1 or type 2 diabetes mellitus (DM), vasodilation was reduced to both aprikalim (maximum dilation, DM(+) 90±2% versus DM(−) 96±1%,P<0.05) and hypoxia (maximum dilation, DM(+) 56±8% versus DM(−) 85±5%,P<0.01) but was not altered to sodium nitroprusside or bradykinin. Baseline myogenic tone and resting membrane potential were not affected by DM. We conclude that DM impairs human coronary arteriolar dilation to KATPopening, leading to reduced dilation to hypoxia. This reduction in KATPfunction could contribute to the greater cardiovascular mortality and morbidity in DM.

ISSN:0009-7330    

出版商:OVID    

年代:2003

数据来源: OVID