2-Deoxyglucose-induced vasodilation and hyperpolarization in rat coronary artery are reversed by glibenclamide

1994 ◽  
Vol 266 (4) ◽  
pp. H1322-H1326 ◽  
Author(s):  
M. A. Conway ◽  
M. T. Nelson ◽  
J. E. Brayden
Keyword(s):  
Coronary Artery ◽  
Potassium Channels ◽  
Coronary Arteries ◽  
Significant Role ◽  
Hypoglycemic Agents ◽  
Myogenic Tone ◽  
Coronary Vasodilation ◽  
Oral Hypoglycemic Agents ◽  
Intracellular Atp ◽  
Independent Mechanism

The mechanisms responsible for coronary vasodilation during ischemia or hypoxia are poorly understood. It has recently been suggested that alterations in intracellular ATP may play a role in this response. We examined whether dilation of isolated coronary arteries in response to metabolic blockade by 2-deoxyglucose, which competitively inhibits glycolysis and glycogenolysis, was sensitive to glibenclamide, an inhibitor of ATP-sensitive potassium channels. Pressurized rat coronary arteries with myogenic tone dilated in response to 2-deoxyglucose by an endothelium-independent mechanism. The dilation was accompanied by a substantial hyperpolarization. Addition of glibenclamide partially reversed this vasodilation and abolished the hyperpolarization. We propose that ATP-sensitive potassium channels play a significant role in the dilator response to 2-deoxyglucose. This may have implications both for ischemia-induced coronary vasodilation and for the use of oral hypoglycemic agents in general.

scholarly journals Role of peroxisome proliferators-activated receptor-gamma in advanced glycation end product-mediated functional loss of voltage-gated potassium channel in rat coronary arteries

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Li ◽  
S.D Gao ◽  
B Hua ◽  
Q.B Liu ◽  
H.R Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Funding Source ◽  
Peroxisome Proliferators ◽  
Advanced Glycation ◽  
Coronary Vasodilation ◽  
Voltage Gated ◽  
Kv Channel ◽  
Ppar Γ

Abstract Background Voltage-gated K+ (Kv) channels in coronary artery smooth muscle cells (CSMCs), especially the major specific Kv1 subfamily, contribute to coronary artery vasodilation. Advanced glycation end products (AGEs) have been strongly implicated in diabetes-related cardiovascular complications. Our previous study showed AGEs can impair Kv channel-mediated coronary vasodilation by reducing Kv channel activity. However, its underlying mechanism remains unclear. Purpose Here, we used isolated rat small coronary arteries (RSCAs) and primary CSMCs to investigate the effect of AGEs on Kv channel-mediated coronary vasodilation and the possible involvement of peroxisome proliferators-activated receptor (PPAR)-γ pathway. Methods RSCAs and primary CSMCs were isolated, cultured and treated with bovine serum albumin (BSA), AGE-BSA, alagrebrium (ALA, AGE cross-linking breaker), pioglitazone (PIO) and/or GW9662, and then divided into the following groups: DMEM, BSA, AGE, AGE+ALA, AGE+PIO, and AGE+PIO+GW9662. Kv channel-mediated coronary vasodilation was analyzed using wire myograph. Histology and immunohistochemistry of RSCAs were performed. Western blot was used to detect the protein expression of RAGE, the major Kv1 channel subunits expressed in CSMCs (Kv1.2/1.5), PPAR-γ, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-2 (NOX-2). Results AGEs markedly reduced forskolin-induced Kv channel-mediated vasodilation of RSCAs by interacting with the receptor for AGEs (RAGE), and ALA or PIO significantly reversed this effect. In both RSCAs and primary CSMCs, AGEs decreased Kv1.2 and Kv1.5 channel protein expression, inhibited PPAR-γ expression, increased RAGE and NOX-2 expression. Treatment with ALA or PIO partially reversed the effects of AGEs on Kv1.2/Kv1.5 expression, accompanied by elevation of PPAR-γ level and diminished oxidative stress. Conclusion AGE/RAGE axis-induced inhibition of PPAR-γ pathway and enhancement of oxidative stress may contribute to AGEs-mediated Kv channel dysfunction and coronary vasodilation in RSCAs. Our results may provide new insights into developing therapeutic strategies to manage diabetic vasculature. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China; Natural Science Foundation of Beijing (7172059)

Extravascular pressure modulates responses of isolated rat coronary arteries to vasodilator, but not vasoconstrictor, stimuli

2006 ◽  
Vol 290 (3) ◽  
pp. H1151-H1156 ◽  
Author(s):  
May Azzawi ◽  
Clare Austin
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Myogenic Tone ◽  
Cardiac Disorders ◽  
Pressure Myograph ◽  
Isolated Rat

The aims of the study were to investigate whether elevated extravascular pressure modulates responses of isolated rat coronary arteries to constrictor and dilator stimuli. Isolated segments of rat coronary artery were mounted in a modified pressure myograph system that allowed independent modulation of both intra- and extravascular pressures. The influence of elevated extravascular pressure on stable levels of myogenic tone and on responses to vasoconstrictor and vasodilator stimuli was investigated at constant overall transmural pressures. Stable levels of myogenic tone were independent of the relative levels of intra- and extravascular pressure, as were responses to depolarization and to addition of the thromboxane agonist U-46619. Elevating extravascular pressure, however, significantly reduced dilatory responses to introduction of intraluminal flow and to addition of endothelium-dependent and endothelium-independent vasodilatory agonists. These results support the notion that elevated extravascular pressure may attenuate responses of coronary arteries to a variety of dilatory stimuli. This finding may be of relevance to cardiac disorders associated with elevated ventricular pressures.

Exercise restores coronary vascular function independent of myogenic tone or hyperglycemic status in db/db mice

2008 ◽  
Vol 295 (4) ◽  
pp. H1470-H1480 ◽  
Author(s):  
Farzad Moien-Afshari ◽  
Sanjoy Ghosh ◽  
Shahrzad Elmi ◽  
Majid Khazaei ◽  
Mohammad M. Rahman ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Endothelial Function ◽  
Coronary Arteries ◽  
Vascular Function ◽  
Essential Elements ◽  
Whole Body ◽  
Myogenic Tone ◽  
Cardiac Events ◽  
Plasma Insulin Levels ◽  
Myogenic Regulation

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a ∼10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.

Nitric Oxide Modulation of Coronary Artery Myogenic Tone in Spontaneously Hypertensive and Wistar—Kyoto Rats

1998 ◽  
Vol 94 (3) ◽  
pp. 225-229 ◽  
Author(s):  
Susana R. Garcia ◽  
Stuart J. Bund
Keyword(s):  
Nitric Oxide ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Nitric Oxide Synthase Inhibitor ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto ◽  
Synthase Inhibitor

1. The endothelium contributes substantially to the modulation of myogenic tone in coronary arteries from spontaneously hypertensive rats (SHR) and Wistar—Kyoto rats (WKY). This study has addressed the contributions of endothelium-derived nitric oxide and cyclo-oxygenase products to this modulation in small coronary arteries (approximately 200 μm internal diameter) from 20-week-old SHR and WKY under pressurized, no-flow conditions in an arteriograph. 2. Active pressure—diameter relationships were uninfluenced by the cyclo-oxygenase inhibitor indomethacin (10 μmol/l) in either rat strain. In the presence of indomethacin and the nitric oxide synthase inhibitor Nω-nitro-l-arginine (l-NNA, 0.1 mmol/l), coronary arteries from SHR and WKY generated significantly greater myogenic tone. This increase in tone was similar in both strains. 3. In endothelium-denuded arteries, indomethacin and l-NNA did not influence tone. 4. Therefore, these results demonstrate that endothelium-derived nitric oxide is basally released to attenuate SHR and WKY coronary artery myogenic tone, whereas endothelium-derived cyclo-oxygenase products have no net vasoactive influence. Additionally, these data suggest that basal nitric oxide-mediated relaxation is normal in SHR coronary arteries and is therefore unlikely to be a pathogenic mechanism in this animal model of hypertension.

Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses to endothelin-1

1992 ◽  
Vol 263 (1) ◽  
pp. H271-H275 ◽  
Author(s):  
C. Jiang ◽  
P. M. Sarrel ◽  
P. A. Poole-Wilson ◽  
P. Collins
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Calcium Influx ◽  
Acute Effect ◽  
Bay K 8644 ◽  
Endothelin 1 ◽  
Independent Mechanism ◽  
Rabbit Coronary Artery ◽  
The Right ◽  
Dose Dependent

We assessed the acute effect of 17 beta-estradiol on coronary artery constrictor responses to endothelin-1. 17 beta-Estradiol significantly shifted endothelin-1, calcium, or BAY K 8644 concentration-dependent contraction curves to the right in endothelium-denuded coronary arteries isolated from nonpregnant female rabbits. The -log 50% effective dose (ED50) of calcium in high KCl medium (100 mM) was 3.8 +/- 0.11 in control and 3.2 +/- 0.1 and 2.8 +/- 0.12 after incubation with 17 beta-estradiol (1 and 10 microM, respectively). The -log ED50 of BAY K 8644 (KCl 15 mM) was 7.8 +/- 0.1 in control and 7.4 +/- 0.08 and 7.2 +/- 0.05 in the presence of 17 beta-estradiol (1 and 10 microM, respectively). The -log ED50 of endothelin-1 was 9.2 +/- 0.08 in control and 8.8 +/- 0.1, 8.4 +/- 0.07, and 8.1 +/- 0.12 after incubation with 17 beta-estradiol (3, 10, and 30 microM, respectively). Similar results were obtained from coronary arteries of male rabbits. These increases of -log ED50 values were significant (P less than 0.05 or 0.01). 17 beta-Estradiol and verapamil induced dose-dependent relaxation in both endothelium-intact or -denuded coronary arteries submaximally precontracted by endothelin-1. NG-monomethyl-L-arginine had no effect on relaxation induced by 17 beta-estradiol, whereas it eliminated relaxation induced by acetylcholine in rings with an intact endothelium. These data suggest that 17 beta-estradiol attenuates the rabbit coronary artery contraction induced by endothelin-1 via an endothelium-independent mechanism, possibly by affecting calcium influx.

Quantification of Coronary Artery Stenosis with 16-Slice MSCT in Patients before CABG Surgery: Comparison to Standard Invasive Coronary Angiography

2005 ◽  
Vol 8 (1) ◽  
pp. 42 ◽  
Author(s):  
C. Probst ◽  
A. Kovacs ◽  
C. Schmitz ◽  
W. Schiller ◽  
H. Schild ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Coronary Angiography ◽  
Coronary Arteries ◽  
Artery Bypass ◽  
Invasive Coronary Angiography ◽  
Bypass Graft ◽  
Heart Association ◽  
Artery Stenosis ◽  
Vessel Disease ◽  
Selective Coronary Angiography

Objective: Invasive, selective coronary angiography is the gold standard for evaluation of coronary artery disease (CAD) and degree of stenosis. The purpose of this study was to compare 3-dimensional (3D) reconstructed 16-slice multislice computed tomographic (MSCT) angiography and selective coronary angiography in patients before elective coronary artery bypass graft (CABG) procedure. Methods: Sixteen-slice MSCT scans (Philips Mx8000 IDT) were performed in 50 patients (42 male/8 female; mean age, 64.44 8.66 years) scheduled for elective CABG procedure. Scans were retrospectively electrocardiogram-gated 3D reconstructed. The images of the coronary arteries were evaluated for stenosis by 2 independent radiologists. The results were compared with the coronary angiography findings using the American Heart Association segmental classification for coronary arteries. Results: Four patients (8%) were excluded for technical reasons. Thirty-eight patients (82.6%) had 3-vessel disease, 4 (8.7 %) had 2-vessel disease, and 4 (8.7%) had an isolated left anterior descending artery stenosis. In the proximal segments all stenoses >50% (56/56) were detected by MSCT; medial segment sensitivity was 97% (73/75), specificity 90.3%; distal segment sensitivity was 90.7% (59/65), specificity 77%. Conclusion: Accurate quantification of coronary stenosis greater than 50% in the proximal and medial segments is possible with high sensitivity and specificity using the new generation of 16-slice MSCTs. There is still a tendency to overestimate stenosis in the distal segments. MSCT seems to be an excellent diagnostic tool for screening patients with possible CAD.

Congenital Left Main Coronary Artery to Coronary Sinus Fistula

2011 ◽  
Vol 14 (4) ◽  
pp. 255 ◽  
Author(s):  
Fotios A. Mitropoulos ◽  
Meletios A. Kanakis ◽  
Periklis A. Davlouros ◽  
George Triantis
Keyword(s):  
Coronary Artery ◽  
Coronary Arteries ◽  
Coronary Sinus ◽  
Left Main Coronary Artery ◽  
Coronary Artery Fistula ◽  
Left Main ◽  
Coronary Fistula ◽  
Excellent Outcome ◽  
Surgical Ligation ◽  
Congenital Coronary Artery Fistula

Congenital coronary artery fistula is an extremely rare anomaly that may involve any of the coronary arteries and any of the cardiac chambers. We report the case of a 14-year-old female patient with a symptomatic congenital coronary fistula starting from the left main coronary artery and draining to the coronary sinus. The patient underwent surgical ligation of the fistula and had an excellent outcome.

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