P707Blockade of cystathionine gamma-lyase increases endothelium-dependent relaxation of aortic smooth muscles in old rats.

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Abstract

Purpose. It is known that aging increases the risk of cardiovascular diseases. One of the reasons is a dysfunction of endothelium that aggravates with age. At the same time we can see more and more publications about cardio- and vasoprotective properties of hydrogen sulfide (H2S). This gas belongs to the family of gas transmitters, such as NO and CO. The uniqueness of gas transmitters consists in their ability to easily penetrate the cellular membranes without binding to any cell surface receptors and to interact directly with the intracellular structures. Cystathionine gamma-lyase (CSE) is the main enzyme for H2S synthesis in blood vessels. The aim of this study was to show the effect of blocking of CSE-associated H2S synthesis pathway upon endothelium-dependent relaxation of aortic smooth muscles (SM) in old animals.

Methods. The samples of aortic tissue of Wistar rats aged 6 (adult) and 24 months (old) (n=16) were subjected to the study. Activation of isolated samples was carried out by adding norepinephrine (NA) 10 M solution to the solution for perfusion. Persistent level of NA-dependent vasoconstriction (a ‘plateau’) was taken as 100 %. It was used as a basis for calculation of the change in the amplitude of the contractile responses of aortic SM tissue to acetylcholine (Ach) 10 M. The activity of CSE was inhibited with propargylglycine (PPG) of 10 M by incubation of aortic tissue segment during 30 min and adding the blocker to NA and Ach-containing solutions for perfusion. H2S was determined by N,N-dimethyl-p-phenylenediamine method, NO de novo synthesis - by NOs activity and nitrite determination.

Results. The experiments on isolated segments of aortic tissue in old rats have shown that the effect of Ach endothelium-dependent vasodilator results in less profound relaxation of aortic SM in old animals (12.4%) compared to adult ones (66.3%). PPG addition resulted in growing aortic SM relaxation amplitude from 12.4% to 49.5%. Using PPG of the same concentration in heart mitochondria resulted in paradoxical changes of some investigated biochemical indicators. First of all, H2S and NO2- pools, which were the oxygenation markers increased rather than decreased from 52% to 111% and from 54 to 141% (of control (in adult animals) level taken as 100%) respectively. Use of PPG resulted also in growing activity of cNOS (from 32 to 92%) and decreasing activity of iNOS (from 763 to 401%).

Conclusions. Therefore, we can state that use of PPG has led us to growing production of two powerful vasodilators - H2S and NO and to the restoration of endothelium-dependent aortic SM vasorelaxation in old animals.

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