scholarly journals THE EFFECT OF PROPARGYLGLYCINE ON THE ENDOTHELIUM-DEPENDENT RELAXATION AND ACTIVITY OF MAIN SOURCES OF SUPEROXIDE ANION GENERATION DURING AGING

2020 ◽  
Vol 66 (4) ◽  
pp. 7-11
Author(s):  
K.O. Drachuk ◽  
◽  
N.A. Dorofeyeva ◽  
V. F. Sagach ◽  
◽  
...  

The objective of the present study was to investigate the effect of propargylglycine (PAG), an inhibitor of the CSE-dependent pathway of hydrogensulfide synthesis, on the endotheliumdependent relaxation of aortic smooth muscle (SM) in old rats. It was found a violation of SM relaxation in this group of animals. The average value of its amplitude was 7.5 ± 1.4% compared with 64.9 ± 3.5% in healthy adult rats. PAG significantly improved endothelium-dependent relaxation in old rats, the average value of its amplitude increased from 7.5 ± 1.4% to 44,5 ± 3,2%. This effect was due to suppression of superoxide anion generation by inhibition of xanthineoxidase activity.

Author(s):  
Konstantin O. Drachuk ◽  
Anatolii V. Kotsuruba ◽  
Olga V. Bazilyuk ◽  
Lyubov G. Stepanenko ◽  
Vadim F. Sagach

1992 ◽  
Vol 49 (3) ◽  
pp. 175-185 ◽  
Author(s):  
Marie-Luce Bochaton-Piallat ◽  
Franoise Gabbiani ◽  
Patricia Ropraz ◽  
Giulio Gabbiani

2002 ◽  
Vol 283 (1) ◽  
pp. H382-H390 ◽  
Author(s):  
Chiwaka Kimura ◽  
Wei Cheng ◽  
Kazunari Hisadome ◽  
Yi-Ping Wang ◽  
Tetsuya Koyama ◽  
...  

We examined the effects of superoxide anion (O[Formula: see text]) generated by xanthine plus xanthine oxidase (X/XO) on the intracellular Ca2+ concentration ([Ca2+]i) and muscle contractility in cultured bovine aortic smooth muscle cells (BASMC). Cells were grown on collagen-coated dish for the measurement of [Ca2+]i. Pretreatment with X/XO inhibited ATP-induced Ca2+ transient and Ca2+release-activated Ca2+ entry (CRAC) after thapsigargin-induced store depletion, both of which were reversed by superoxide dismutase (SOD). In contrast, Ca2+ transients induced by high-K+ solution and Ca2+ ionophore A-23187 were not affected by X/XO. BASMC-embedded collagen gel lattice, which was pretreated with xanthine alone, showed contraction in response to ATP, thapsigargin, high-K+ solution, and A-23187. Pretreatment of the gel with X/XO impaired gel contraction not only by ATP and thapsigargin, but also by high-K+ solution and A-23187. The X/XO-treated gel showed normal contraction; however, when SOD was present during the pretreatment period. These results indicate that O[Formula: see text] attenuates smooth muscle contraction by impairing CRAC, ATP-induced Ca2+ transient, and Ca2+ sensitivity in BASMC.


2006 ◽  
Vol 290 (5) ◽  
pp. C1341-C1349 ◽  
Author(s):  
Jyoti Pande ◽  
Kanwaldeep K. Mallhi ◽  
Ahilya Sawh ◽  
Magdalena M. Szewczyk ◽  
Fiona Simpson ◽  
...  

Plasma membrane Ca2+ pumps (PMCA) that expel Ca2+ from cells are encoded by four genes (PMCA1–4). In this study, we show that aortic endothelium and smooth muscle differ in their PMCA isoform mRNA expression: endothelium expressed predominantly PMCA1, and smooth muscle expressed PMCA4 and a lower level of PMCA1. In this study, we report a novel peptide (caloxin 1b1, obtained by screening for binding to extracellular domain 1 of PMCA4), which inhibited PMCA extracellularly, selectively, and had a higher affinity for PMCA4 than PMCA1. It inhibited the PMCA Ca2+-Mg2+-ATPase activity in leaky erythrocyte ghosts (mainly PMCA4) with a Ki value of 46 ± 5 μM, making it 10× more potent than the previously reported caloxin 2a1. It was isoform selective because it inhibited the PMCA1 Ca2+-Mg2+-ATPase in human embryonic kidney-293 cells with a higher Ki value (105 ± 11 μM) than for PMCA4. Caloxin 1b1 was selective in that it did not inhibit other ATPases. Because caloxin 1b1 had been selected to bind to an extracellular domain of PMCA, it could be added directly to cells and tissues to examine its effects on smooth muscle and endothelium. In deendothelialized aortic rings, caloxin 1b1 (200 μM) produced a contraction. It also increased the force of contraction produced by a submaximum concentration of phenylephrine. In aortic rings with endothelium intact, precontracted with phenylephrine and relaxed partially with a submaximum concentration of carbachol, caloxin 1b1 increased the force of contraction rather than potentiating the endothelium-dependent relaxation. In cultured cells, caloxin 1b1 increased the cytosolic [Ca2+] more in arterial smooth muscle cells than in endothelial cells. Thus caloxin 1b1 is the first highly selective extracellular PMCA inhibitor that works better on vascular smooth muscle than on endothelium.


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