Antenatal Dexamethasone Exposure Altered Micro-Vessel Functions Via Activating IP3R1 and L-Type Cav1.2 Channels in Offspring Rats

2022 ◽  
Author(s):  
Ting Xu ◽  
Jiahui Lei ◽  
Lingjun Li ◽  
Bingyu Ji ◽  
Meng Zhao ◽  
...  
Keyword(s):  

Planta Medica ◽  
2020 ◽  
Vol 86 (09) ◽  
pp. 631-642
Author(s):  
Watcharee Waratchareeyakul ◽  
Fabio Fusi ◽  
Miriam Durante ◽  
Amer Ahmed ◽  
Walter Knirsch ◽  
...  

AbstractFive compounds, 3,4′-dihydroxy-3′,5,5′-trimethoxydihydrostilbene, 1; 3,4′-ihydroxy-3′,5′-dimethoxydihydrostilbene, 2; 3,4′-dihydroxy-5,5′-dimethoxydihydrostilbene, 3; 9,10-dihydro-2,7-dihydroxy-4,6-dimethoxyphenanthrene, 4; and the previously unreported 1,2,6,7-tetrahydroxy-4-methoxyphenanthrene, 5 were isolated from the South American orchid, Brasiliorchis porphyrostele. An in-depth analysis of their vascular effects was performed on in vitro rat aorta rings and tail main artery myocytes. Compounds 1 – 4 were shown to possess vasorelaxant activity on rings pre-contracted by the α 1 receptor agonist phenylephrine, the CaV1.2 stimulator (S)-(−)-Bay K 8644, or depolarized with high K+ concentrations. However, compound 5 was active solely on rings stimulated by 25 mM but not 60 mM K+. The spasmolytic activity of compounds 1 and 4 was significantly affected by the presence of an intact endothelium. The KATP channel blocker glibenclamide and the KV channel blocker 4-aminopyridine significantly antagonized the vasorelaxant activity of compounds 4 and 1, respectively. In patch-clamp experiments, compounds 1 – 4 inhibited Ba2+ current through CaV1.2 channels in a concentration-dependent manner, whereas neither compound 4 nor compound 1 affected K+ currents through KATP and KV channels, respectively. The present in vitro, comprehensive study demonstrates that Brasiliorchis porphyrostele may represent a source of vasoactive agents potentially useful for the development of novel antihypertensive agents that has now to be validated in vivo in animal models of hypertension.



Planta Medica ◽  
2020 ◽  
Vol 86 (04) ◽  
pp. 284-293 ◽  
Author(s):  
Nguyen Manh Cuong ◽  
Ninh The Son ◽  
Ngu Truong Nhan ◽  
Pham Ngoc Khanh ◽  
Tran Thu Huong ◽  
...  

Abstract Dalbergia species heartwood, widely used in traditional medicine to treat various cardiovascular diseases, might represent a rich source of vasoactive agents. In Vietnam, Dalbergia tonkinensis is an endemic tree. Therefore, the aim of the present work was to investigate the vascular activity of R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol isolated from the heartwood of D. tonkinensis and to provide circular dichroism features of its R absolute configuration. The vascular effects of R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol were assessed on the in vitro mechanical activity of rat aorta rings, under isometric conditions, and on whole-cell Ba2+ currents through CaV1.2 channels (IBa1.2) recorded in single, rat tail main artery myocytes by means of the patch-clamp technique. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol showed concentration-dependent, vasorelaxant activity on both endothelium-deprived and endothelium intact rings precontracted with the α 1 receptor agonist phenylephrine. Neither the NO (nitric oxide) synthase inhibitor Nω-nitro-L-arginine methyl ester nor the cyclooxygenase inhibitor indomethacin affected its spasmolytic activity. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol-induced vasorelaxation was antagonized by (S)-(−)-Bay K 8644 and unaffected by tetraethylammonium plus glibenclamide. In patch-clamp experiments, R-(−)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol inhibited IBa1.2 in a concentration-dependent manner and significantly decreased the time constant of current inactivation. R-(−)-3′-Hydroxy-2,4,5-trimethoxydalbergiquinol likely stabilized the channel in its closed state, as suggested by molecular modelling and docking simulation to the CaV1.2 channel α 1c subunit. In conclusion, D. tonkinensis species may represent a source of agents potentially useful for the development of novel antihypertensive drugs.



2003 ◽  
Vol 100 (22) ◽  
pp. 13093-13098 ◽  
Author(s):  
J. T. Hulme ◽  
T. W.- C. Lin ◽  
R. E. Westenbroek ◽  
T. Scheuer ◽  
W. A. Catterall


2010 ◽  
Vol 98 (3) ◽  
pp. 16a
Author(s):  
Matthew D. Fuller ◽  
Todd Scheuer ◽  
William A. Catterall
Keyword(s):  


Molecules ◽  
2019 ◽  
Vol 24 (15) ◽  
pp. 2748 ◽  
Author(s):  
Fernando Romero ◽  
Javier Palacios ◽  
Ignacio Jofré ◽  
Cristian Paz ◽  
Chukwuemeka R. Nwokocha ◽  
...  

Alkaloids derived from plants have shown great medicinal benefits, and are often reported for their use in cardiovascular disease management. Aristotelia chilensis (Molina) Stuntz (Maqui) has shown important medicinal properties in traditional useage. In this study, we evaluated the effect of the indole-alkaloid aristoteline (ARI), isolated from leaves of Maqui, on vascular reactivity of isolated aortic rings from normotensive rats. ARI induced relaxation (100%) in a concentration-dependent manner in intact or denuded-endothelium aortic rings pre-contracted with phenylephrine (PE; 1 μM). However, a specific soluble guanylyl cyclase inhibitor (ODQ; 1 μM) significantly reduced the relaxation to ARI in aortic rings pre-contracted with PE. In the presence of ARI, the contraction induced by KCl or PE was significantly (p < 0.05) decreased. Interestingly, the potassium channel blockade with 10 μM BaCl2 (Kir), 10 μM glibenclamide (KATP), 1 mM tetraethylammonium (TEA; KCa1.1), or 1 mM 4-aminopyridine (4-AP; Kv) significantly (p < 0.05) reduced the ARI-induced relaxation. ARI significantly (p < 0.05) reduced the contractile response to agonist of CaV1.2 channels (Bay K8644; 10 nM), likely reducing the influx of extracellular calcium through plasma membrane. The mechanisms associated with this process suggest an activation of the potassium channels, a calcium-induced antagonism and endothelium independent vasodilation that possibly involves the nitric oxide-independent soluble guanylate cyclase pathway.



2003 ◽  
Vol 84 (6) ◽  
pp. 3662-3678 ◽  
Author(s):  
Gonzalo Ferreira ◽  
Eduardo Ríos ◽  
Nicolás Reyes


2020 ◽  
Vol 41 (9) ◽  
pp. 1158-1166 ◽  
Author(s):  
Fabio Fusi ◽  
Alfonso Trezza ◽  
Giampietro Sgaragli ◽  
Ottavia Spiga ◽  
Simona Saponara ◽  
...  


2020 ◽  
Vol 118 (3) ◽  
pp. 499a
Author(s):  
Federica Steccanella ◽  
Nicoletta Savalli ◽  
Marina Angelini ◽  
Alan Neely ◽  
Riccardo Olcese


2016 ◽  
Vol 291 (40) ◽  
pp. 21148-21159 ◽  
Author(s):  
Javier Ávila-Medina ◽  
Eva Calderón-Sánchez ◽  
Patricia González-Rodríguez ◽  
Francisco Monje-Quiroga ◽  
Juan Antonio Rosado ◽  
...  


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