Flow-mediated vasodilation of human epicardial coronary arteries: effect of inhibition of nitric oxide synthesis

AbstractObjectives. This study sought to investigate the role of nitric oxide, an endothelium-derived relaxing factor, in flow-mediated vasodilation in human epicardial coronary arteries.Background. Endothelium-derived relaxing factors may be released from the coronary artery endothelium in response to increases in blood flow.Methods. We studied the effect of the nitric oxide synthesis inhibitor NG-monomethyl-l-arginine (l-NMMA) on the flow-mediated vasodilation of epicardial coronary arteries in 12 patients, using quantitative angiographic and Doppler flow velocity measurements. Adenosine at 100 μg/min was infused into the left anterior descending coronary artery to test the dilator response of the proximal artery to increases in blood flow. Acetylcholine at 3 and 30 μg/min was infused into the left coronary ostium to determine endothelium-dependent vasodilation of the proximal left anterior descending artery. Adenosine and acetykholine were infused before and after the intracoronary infusion ofl-NMMA (25 μg/min for 5 min).Results. Infusion ofl-NMMA caused a significant decrease in the baseline diameter of the proximal left anterior descending artery (from 2.90 ± 0.14 to 2.74 ± 0.13 mm [mean ± SEM], p < 0.01). Adenosine increased coronary blood flow Wore and afterl-NMMA (+3995 ± 27.5% and +511.9 ± 33.3%, respectively). Flow-mediated vasodilation was observed in the proximal left anterior descending artery before and afterl-NMMA (+9.2 ± 1.5%, p < 0.01 and +8.6 ± 2.1%, p < 0.01, respectively). A dose of 3 μg/min of acetylcholine significantly dilated the proximal left anterior descending artery beforel-NMMA (+7.6 ± 1.0%, p < 0.01), but acetylcholine-induced vasodilation was attenuated afterl-NMMA (−1.8 ± 1.0%).Conclusions. Our data suggest that nitric oxide modulates basal coronary artery tone but that mediators other than nitric oxide may be responsible for the flow-mediated vasodilation of human epicardial coronary arteries

The Role for HNF-1β-Targeted Collectrin in Maintenance of Primary Cilia and Cell Polarity in Collecting Duct Cells

Collectrin, a homologue of angiotensin converting enzyme 2 (ACE2), is a type I transmembrane protein, and we originally reported its localization to the cytoplasm and apical membrane of collecting duct cells. Recently, two independent studies of targeted disruption of collectrin in mice resulted in severe and general defects in renal amino acid uptake. Collectrin has been reported to be under the transcriptional regulation by HNF-1α, which is exclusively expressed in proximal tubules and localized at the luminal side of brush border membranes. The deficiency of collectrin was associated with reduction of multiple amino acid transporters on luminal membranes. In the current study, we describe that collectrin is a target of HNF-1β and heavily expressed in the primary cilium of renal collecting duct cells. Collectrin is also localized in the vesicles near the peri-basal body region and binds to γ-actin-myosin II-A, SNARE, and polycystin-2-polaris complexes, and all of these are involved in intracellular and ciliary movement of vesicles and membrane proteins. Treatment of mIMCD3 cells with collectrin siRNA resulted in defective cilium formation, increased cell proliferation and apoptosis, and disappearance of polycystin-2 in the primary cilium. Suppression of collectrin mRNA in metanephric culture resulted in the formation of multiple longitudinal cysts in ureteric bud branches. Taken together, the cystic change and formation of defective cilium with the interference in the collectrin functions would suggest that it is necessary for recycling of the primary cilia-specific membrane proteins, the maintenance of the primary cilia and cell polarity of collecting duct cells. The transcriptional hierarchy between HNF-1β and PKD (polycystic kidney disease) genes expressed in the primary cilia of collecting duct cells has been suggested, and collectrin is one of such HNF-1β regulated genes

Comparison of Properties of Slow Pathway Potential between Successful and Unsuccessful Radiofrequency Applications in Patients who Underwent Catheter Ablation for Atrioventricular Nodal Reentrant Tachycardia

Findings concerning selective slow pathway radiofrequency ablation for atrioventricular nodal reentrant tachycardia (A VNRT) using the slow pathway potential (SPP) guided method are reported. The electrogram at the SPP recording site showed double potentials consisting of the atrial potential (A) and SPP. However, SPP is usually recorded widely in the right atrial posteroseptal region. To examine whether there was any characteristic marker in the electrogram at the SPP recording site specific to successful RF application, the properties of SPP and its anatomical locations in both successful (S) (38 sites) and unsuccessful (UN) (28 sites) application sites were analyzed in 38 patients who underwent SPP-guided ablation. The distance between the upper margin of the coronary sinus ostium (UCSO) and the ablation catheter (ABL) (DUCSO-ABL) was shorter in S than in UN (2.3 ± 6.3 mm vs. 9.0 ± 5.2 mm below the level of UCSO, p < 0.001). The interval between A and SPP (A-SPP) was longer in S than in UN (44.2 ± 9.9 msec vs. 24.0 ± 7.0 msec, p < 0.001). RF applications at the more anterior sites with longer A-SPP were more successful than at other sites. The sensitivity and specificity of A-SPP (more than 40 msec) were superior to those of DUCSO-ABL (within 5 mm) as the marker for the successful application (sensitivity; 73.7% v.s. 68.4%, specificity; 100% v.s. 82.1 %, respectively). In conclusion, the sites with longer A-SPP might be specific for successful ablation

Structural Characteristics of Koch's Triangle in Patients with Atrioventricular Node Reentrant Tachycardia

The aim of this study is to investigate whether patients with atrioventricular node reentrant tachycardia (AVNRT) present different structural characteristics of Koch's triangle from patients with atrioventricular (AV) reentrant tachycardia and other control patients. Fifty-eight patients with arrhythmia or chest pain underwent selective coronary sinus angiography so that the diameter of the coronary sinus could be measured. The patients with arrhythmia also underwent electrophysiological study and measurement of the height of Koch's triangle. Patients with AVNRT had large coronary sinus ostial diameters compared with patients with AV reentrant tachycardia and those with chest pain (13.6 ± 2.2 mm vs. 10.6 ± 2. 7 mm [p < 0.005] and 10.0 ± 2.1 mm [p < 0.002], respectively), while there were no differences in distal diameter. The ostial diameter in patients with dual AV node pathways but noninducible AVNRT (11.8 ± 1.5 mm) tended to be smaller than that in patients with AVNRT. No differences in the height of Koch's triangle and electrophysiological characteristics, including AV node properties, were found among the study groups. In conclusion, an increased size of the coronary sinus ostium (the base of Koch's triangle) is a structural characteristic in patients with AVNRT and may be the substrate needed for the appearance of AVNRT