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International Journal of Physiology and Pathophysiology
SJR: 0.116

ISSN 印刷: 2155-014X
ISSN オンライン: 2155-0158

Archives: Volume 1, 2010 to Volume 9, 2018

International Journal of Physiology and Pathophysiology

DOI: 10.1615/IntJPhysPathophys.v2.i1.70
pages 69-77

Vasodilatation Effects of Fluorine- Containing KATP Channels Opener of Flocalin

Ruslan B. Strutynskyi
Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv

要約

At present all greater attention of the researchers attracts of ATP-sensitive potassium channels. These are membrane channels somewhat especial - they are opened at reduction energy resource, in particular ATP, in cells. Their activation has strong defensive importance, particularly under hypoxia and ischemia of tissues, and is one of main endogenous a mechanism of protection of the cells. At hypoxia and ischemia of myocardium, activation of ATP-sensitive potassium channels results because of a reduction in a number of energy substrates and serves a strong endogenous of mechanisms of cardioprotection. A decrease in content of intracellular calcium results in vasodilatation of the coronary and peripheral vessels, as well as antispasmic effects on smooth muscle of various organs. What turned out to be, open these channels possible and pharmacological way, by means of their openers. To pharmacological facility, which open the potassium channels pertains the new fluorine-containing opener flocalin, which and is an object of our studies. Flocalin has been created as a result of the long- term collaboration of Bogomoletz Physiology Institute and Organic Chemistry Institute of the NAS of Ukraine for the purpose of development and introduction of the new drug in clinical implication. Flocalin is agent from cyanoguanidines family and is the sarcolemmal and mitochondrial ATP-sensitive potassium channel opener. Purpose of our work was a study of vasodilatation effects of flocalin in condition in vivo. Flocalin was introduced in intravenous (the system arterial pressure (SAP) was measured) and in perfusion by blood of hip artery (the perfusion pressure measured in her) in dose 0.01 - 1.5 mg/kgs. In experiments on greater animals (the anesthetic dogs) was shown that amplitude and duration of hypotension effect of flocalin corresponded of introduced dose - the higher dose, the greater and longer effect. Thereby, is shown, he has expressed dose-dependent vasodilatation effects, which practically do not differ from effect of the known opener ATP-sensitive potassium channel pinacidil. Flocalin is a fluorine-containing analogue pinacidil. However follows to notice that investigations flocalin on innocence has shown that he in 3.5 times less toxic, than pinacidil. The registration of system arterial pressure has shown that under intravenous introduction of threshold dose of flocalin is 0.05 mg/kgs - dilatation reaction by duration around three minutes and amplitude (9.5 ± 2.0)% (n = 7, P < 0.05). Introduction of flocalin in dose 0.5 mg/kgs and above, reduced SAP more vastly - on 37% and above. Herewith 0.5; 0.75; 1.0 and 1.5 mg/kgs reduced his from source level in the mean on (42 ± 6) (n = 5, Р < 0.05); 44 ± 5 (n = 3, Р < 0.05); 44 ± 5 (n = 5, Р < 0.05) and 66.28 mm Hg ± 3.15 mm Hg (n = 3, Р < 0.05) accordingly. Under intravenous introduction the greater doses of flocalin (0.75 - 1.5 mg/kgs) enough often SAP reduce to 40 - 50 mm Hg. However such dangerous reduction of the arterial pressure was comparatively short and lasted not more than 15 minutes, after outflow which it was gradually (usually during hour) restored. Introduction of flocalin in hip artery and measurement of perfusion pressure in her has shown practically similar results. In our view optimal cardioprotective doses of flocalin - 0.1 and 0.2 mg/kgs (preischemic introduction which in experiment with acute ischemia and reperfusion of myocardium reduces of infarct size of myocardium within 37- 40%) realistically reduce SAP in the first 5 and 25 mines accordingly. In spite of the fact that hypotension effect of flocalin in dose 0.2 mg/kgs in twice greater and in 5 times longer than under 0.1 mg/kgs, cardioprotective effects under their introduction in the experiments with ischemia-reperfusion of the myocardium practically do not differ. This can be indicative of possible absence of direct correlation between preischemic reduction of the arterial pressure and protection of the myocardium against ischemia and reperfusion of injuries under pharmacological preconditioning caused flocalin. Probably, more important role in this instance belongs to vasodilatation of coronary vessels of heart and prevention of the development of their vasoconstriction under reperfusion of ischemic myocardium. Thus, for the reason minimum of influence upon hemodynamic parameters and start of cardioprotective antiischemic mechanisms in experiments with ischemia- reperfusion of myocardium in vivo, flocalin, probably, necessary to use in dose not exceeding 0.2 mg/kgs.