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 EFFECT OF PROPARGYLGLYCINE UPON CARDIOHEMODYNAMICS IN OLD RATSK.O. Drachuk, N.A. Dorofeyeva, A.V. Kotsjuruba, V.F. Sagach 
O.O. Bogomoletz Institute of physiology NAS of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz61.04.035 
  
 
 
Abstract
Aging increases the risk of cardiovascular diseases. The
objective of this study was to show the effect of propargylglycine
(PPG) upon cardiohemodynamics in old rats. We used
pressure-volume (PV) conductance catheter system (Millar
Instruments, USA) in order to evaluate systolic and diastolic
function in vivo. It has been shown that introducted PPG
(11,31 mg/kg) decrises both arterial stiffness (by 1,5 times)
and end-diastolic stiffness (by 2,1 times) in old rats. Using PPG 
in heart mitochondria resulted in increasing levels of H2S (by
112%), NO2
-
(by 162%) and in growing activity of cNOS (by
3 times). Additionally, PPG decreased the mitochondrial pools
of the uric acid, the marker of the superoxide (*O2
-
) formation
and of the ATP degradation. These results suggest that PPG
activates alternative ways of H2S synthesis, stimulates the
NO and H2S synthesis and suppresses the ATP degradation
and *O- formation. These actions of PPG improve arterial
stiffness and end-diastolic stiffness.
 
Keywords: 
aging; cardiohemodynamic; hydrogen sulfide; propargylglycine; oxidative stress; uric acid
References
 
Streeter E, HH Ng, Hart JL. Hydrogen sulfide as a vasculoprotective factor. Med Gas Res. 2013;3(1):1–9.
CrossRef
PubMed PubMedCentralKondo K, Bhushan S, King AL, Prabhu SD, Hamid T, Koenig S, et al. H2S protects against pressure overloadinduced heart failure via upregulation of endothelial nitric oxide synthase. Circulation. 2013;127(10):1116–27.
CrossRef
PubMed PubMedCentralZhou X, An G, Chen J. Hydrogen sulfide improves left ventricular function in smoking rats via regulation of apoptosis and autophagy. Apoptosis. 2014 Jun;19(6):998-1005.Gil V, Gallego D, Jiménez M. Effects of inhibitors of hydrogen sulphide synthesis on rat colonic motility. Br J Pharmacol. 2011 Sep; 164(2b):485–98.Xue H, Yuan P, Ni J, Li C, Shao D, Liu J, et al. H(2) S inhibits hyperglycemia-induced intrarenal reninangiotensin system activation via attenuation of reactive oxygen species generation. PLoS One. 2013;8(9).Sagach VF, Shimanskaya TV, Goshovska YV. Effects of stimulation and blockade of the synthesis of endogenous hydrogen sulfide at myocardial ischemia-reperfusion. Fiziol Zh. 2013;59(4):8–15[Ukrainian].Dorofeyeva NA, Kuzmenko MA, Sagach VF. Effects of hydrogen sulfide donor on the heart function of spontaneously hypertensive rats. TMB Visnyk. 2012;15(3):92–4[Ukrainian].Drachuk KO, Kotsjuruba AV, Bazilyuk OV, Stepanenko LG, Sagach VF. Propargylglycine restores endothelium-dependent relaxation of aortic smooth muscle in old rats. Fiziol Zh 2014; 60(4):3–10 [Ukrainian].Pacher P, Nagayama T, Mukhopadhyay P, Batkai S, Kass DA. Measurement of cardiac function using pressurevolume conductance catheter technique in mice and rats. Nat Protoc. 2008;9:1422–34.
CrossRef
PubMed PubMedCentralSharipov RR, Kotsiuruba AV, Kopyak BS, Sagach VF. Induction of oxidative stress in heart mitochondria of brain focal ischemia-reperfusion and protective effect of ecdysterone. Fiziol Zh. 2014;60(3):11–17 [Ukrainian].López-Andrés N, Calvier L, Labat C, Fay R, Díez J, Benetos A, et al. Absence of cardiotrophin 1 is associated with decreased age-dependent arterial stiffness and increased longevity in mice. Hypertension. 2013;61(1):120–9.
CrossRef
PubMedDorofeyeva NA, Drachuk KO, Sagach VF. Cardiohemodynamics and efficiency of Frank–Starling mechanism during aging. Fiziol Zh. 2014;60(6):22–6 [Ukrainian].Asp ML, Martindale JJ, Heinis FI, Wang W, Metzger JM. Calcium mishandling in diastolic dysfunction: mechanisms and potential therapies. Biochim Biophys Acta. 2013;1833(4):895-900.
CrossRef
PubMed PubMedCentralDai DF, Santana LF, Vermulst M, Tomazela DM, Emond MJ, MacCoss MJ, et al. Overexpression of catalase targeted to mitochondria attenuates murine cardiac aging. Circulation. 2009;119(21):2789-97.
CrossRef
PubMed PubMedCentralShareef MA, Anwer LA, Poizat C. Cardiac SERCA2A/B: therapeutic targets for heart failure. Eur J Pharmacol. 2014;724:1-8.
CrossRef
PubMedGouspillou G, Bourdel-Marchasson I, Rouland R, Calmettes G, Biran M, Deschodt-Arsac V, et al. Mitochondrial energetics is impaired in vivo in aged skeletal muscle. Aging Cell. 2014;13(1):39–48.
CrossRef
PubMed PubMedCentralSalloum FN, Sturz GR, Yin C, Rehman S, Hoke NN, Kukreja RC, et al. Beetroot juice reduces infarct size and improves cardiac function following ischemiareperfusion injury: Possible involvement of endogenous H2S. Exp Biol Med (Maywood). 2014;doi:10. 1177/1535370214558024. PMID:25361774.King AL, Polhemus DJ, Bhushan S, Otsuka H, Kondo K, Nicholson CK, et al. Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent. Proc Natl Acad Sci. 2014;111(8):3182-7.
CrossRef
PubMed PubMedCentral |