scholarly journals Effect of adenosine antagonism on metabolically mediated coronary vasodilation in humans

1994 ◽  
Vol 23 (6) ◽  
pp. 1421-1426 ◽  
Author(s):  
James D. Rossen ◽  
Helgi Oskarsson ◽  
Robert L. Minor ◽  
Charlotte L. Talman ◽  
Michael D. Winniford
2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Li ◽  
S.D Gao ◽  
B Hua ◽  
Q.B Liu ◽  
H.R Liu ◽  
...  

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)


2016 ◽  
Vol 43 (8) ◽  
pp. 1491-1492
Author(s):  
Raffaele Giubbini ◽  
Francesco Bertagna

2001 ◽  
Vol 169 (1) ◽  
pp. 177-183 ◽  
Author(s):  
K Terui ◽  
A Higashiyama ◽  
N Horiba ◽  
KI Furukawa ◽  
S Motomura ◽  
...  

Corticotropin-releasing factor (CRF) has a coronary vasodilator effect and a positive inotropic effect on the isolated rat heart. Recently, expression of CRF receptor type 2 (CRF-R2) has been demonstrated in the heart. In addition, urocortin (Ucn), a new member of the CRF family, has been reported to have much greater affinity for CRF-R2 than CRF. It is suggested that the cardiac effects of Ucn may be more potent than those of CRF. We compared the effect of Ucn with that of CRF on isolated rat heart. The effects of Ucn were then analyzed to determine whether these effects were mediated by CRF receptors and/or any other mediators under the following conditions: perfusion buffer containing (1) alpha-helical CRF 9-41, (2) indomethacin, (3) N(G)-nitro-l -arginine methylester and (4) propranolol. Ucn exhibited a greater effect with a longer duration of action than CRF. Indomethacin significantly attenuated the vasodilator effects of Ucn (P<0.05). CRF receptor antagonist diminished both coronary vasodilation and the positive inotropic effects of Ucn (P<0.05). These results suggest that the cardiac effects of Ucn may be mediated by a CRF receptor, and prostaglandins may be involved in the vasodilator effect.


1996 ◽  
Vol 27 (2) ◽  
pp. 287
Author(s):  
Eduardo Aptecar ◽  
Patrick Dupouy ◽  
Christophe Benvenuti ◽  
Emmanuel Teíger ◽  
Herbert Geschwind ◽  
...  

1989 ◽  
Vol 10 (suppl F) ◽  
pp. 147-152 ◽  
Author(s):  
S. Jost ◽  
W. Rafflenbeul ◽  
B. Mogwitz ◽  
U. Nellessen ◽  
C. Bossaller ◽  
...  

Circulation ◽  
2000 ◽  
Vol 101 (3) ◽  
pp. 311-317 ◽  
Author(s):  
Masafumi Kitakaze ◽  
Hiroshi Asanuma ◽  
Seiji Takashima ◽  
Tetsuo Minamino ◽  
Yasunori Ueda ◽  
...  

2005 ◽  
Vol 46 (4) ◽  
pp. 534-539 ◽  
Author(s):  
Kentaro Ueda ◽  
Hiroki Teragawa ◽  
Masashi Kimura ◽  
Keiji Matsuda ◽  
Yukihito Higashi ◽  
...  

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