摘要:

Background—Previous reports from our group have shown that 17&bgr;-estradiol reduces the synthesis and activity of inducible nitric oxide synthase (iNOS) in rat aortic smooth muscle cells (SMC) in response to inflammatory mediators. In this study, we investigated the effect of 17&bgr;-estradiol on iNOS function in aortic SMC from streptozotocin-diabetic rats.Methods and Results—Comparative analysis of NO release and of iNOS mRNA and protein content after 24-hour stimulation with a cytokine mixture revealed milder iNOS activation in diabetic than in control SMC. Furthermore, 17&bgr;-estradiol dose-dependently blocked iNOS synthesis and activity in control but not in diabetic SMC. The defective estrogen response in diabetic SMC at 24 hours could not be attributed to reduced expression of estrogen receptors (ER). In fact, mRNA and protein levels of ER&agr; and, to a greater extent, of ER&bgr;, were increased in diabetic compared with nondiabetic SMC. Cytokines decreased ER&agr; and ER&bgr; expression in both groups. However, 17&bgr;-estradiol dose-dependently restored the expression of ER&agr; but further downregulated that of ER&bgr;, indicating a differential regulation of ER isoforms.Conclusions—Estrogenic control of iNOS was impaired in diabetic SMC. This was associated with a larger increase of ER&bgr; than of ER&agr; protein, whereas 17&bgr;-estradiol regulated the two isoforms in an opposite fashion. Thus, modifications in the estrogen modulation of iNOS and in the expression pattern of ER may be involved in diabetic vascular dysfunction.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Noninvasive techniques for detecting acute cardiac transplant rejection are limited. We hypothesized that ultrasound contrast microbubbles targeted to the endothelial cell (EC) inflammatory marker intercellular adhesion molecule-1 (ICAM-1) would selectively bind to rejecting versus nonrejecting myocardium and that myocardial contrast echocardiography can therefore detect acute rejection.Methods and Results—Lipid-based microbubbles were conjugated to anti-rat ICAM-1 (MBICAM) or isotype control antibody (MBControl). In vitro MBICAMadhesion to cultured rat ECs, as assessed in a parallel plate flow apparatus, was greater to inflammatory versus normal ECs (11±3 versus 3±2 microbubbles/EC,P<0.005). In vivo abdominal heterotopic heart transplantation was performed in rats (rejection group: Brown Norway to Lewis strain; control group: Lewis to Lewis or Brown Norway to Brown Norway). Triggered myocardial contrast echocardiography was performed during intravenous MBICAMor MBControl(2.5×106) injection on postoperative day 5. Myocardial videointensity from adhered MBICAMwas significantly higher in rejecting (n=8) versus control (n=7) rats (10±4 versus 1±4 U,P=0.01). Postmortem histology showed normal myocardium in control rats, whereas allograft myocardium demonstrated grade III to IV rejection and strong immunohistochemical ICAM-1 staining.Conclusions—Preferential adherence of ICAM-1-targeted microbubbles to rejecting versus nonrejecting rat cardiac transplant myocardium can be detected ultrasonically. Targeted microbubbles may thus offer a noninvasive ultrasound imaging technique for the detection of acute cardiac transplant rejection and other processes characterized by endothelial dysfunction.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—This study tested the hypothesis that &bgr;1-adrenoreceptor blockade modulates the angiotensin II (Ang II)–evoked neural release of norepinephrine (NE) and epinephrine (Epi) into the cardiac interstitial fluid (ISF) space in experimentally induced mitral regurgitation (MR) in the dog.Methods and Results—Normal dogs (n=8) were compared with dogs with MR of 2 (n=8) and 4 (n=6) weeks’ duration and with dogs with MR treated with &bgr;1-receptor blockade (RB; extended-release metoprolol succinate, 100 mg QD; MR+&bgr;1-RB) that was started 24 hours after MR induction for 2 (n=6) and 4 weeks (n=8). Left ventricular end-diastolic dimension increased 20% as plasma Ang II levels increased >5-fold in both MR and MR+&bgr;1-RB dogs at 2 and 4 weeks. Ang II infusion into the left atrium produced increases in ISF NE and Epi in normal dogs, which were further increased in 2- and 4-week MR dogs but were restored to normal in 4-week MR+&bgr;1-RB dogs. Ang II infusion produced 4-fold increases in circulating NE and Epi in 2- and 4-week MR dogs that returned to normal in 4-week+&bgr;1-RB dogs. Left ventricular angiotensin-converting enzyme activity and ISF Ang II were increased in 4-week MR dogs but were decreased in 4-week MR+&bgr;1-RB dogs.Conclusions—&bgr;1-RB decreases renin-angiotensin system sympathostimulation and activation by attenuating the Ang II–mediated NE and Epi release into the cardiac ISF and circulation and by decreasing left ventricular angiotensin-converting enzyme expression in the early phases of volume overload.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—The anatomic-electrophysiological correlation of AV nodal reentry is unclear. To localize reentrant circuits during atrial and ventricular echoes and to characterize sites of slow conduction and block, we correlated histology with electrophysiology of the AV node.Methods and Results—In 10 isolated dog hearts, extracellular electrical activity was recorded in Koch’s triangle at 208 or 247 sites (interelectrode distance, 0.5 and 0.3 mm) after removal of 0.7 to 1.5 mm of overlying atrial tissue. Resection did not affect refractory periods. Five hearts were subjected to histology. Complete atrial echoes were induced in 1 heart, incomplete atrial echoes in 5 hearts. Unidirectional conduction block occurred at the atrial–transitional cell junction in the superior area. Zones of slow conduction arose at the atrial–transitional or the transitional–compact node junction in the inferior area. Complete reentrant circuits of ventricular echoes were obtained in 5 hearts. Unidirectional conduction block occurred at the compact node–transitional cell junction in the superior area. Localized zones of slow conduction arose at the junctions between the different types of tissue in the inferior area.Conclusions—In the dog heart, tissue architecture and functional dissociation between the inferior and the superior region of the AV node enable dual physiology and reentry. Slow conduction and functional conduction block occur at the junctions between the different types of tissue in the AV nodal area. Atrial echoes were enabled by conduction block at the atrial-transitional cell junction, whereas during ventricular echoes conduction block occurred at the compact node-transitional cell junction.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID