PHARMACEUTICAL ACTIVATORS OF ATP-DEPENDENT POTASSIUM CHANNELS AS POTENTIAL NEPHROPROTECTORS AGAINST GLOMERULAR AND TUBULAR DAMAGE TO THE NEPHRON (REVIEW).

Considering the incidence, high risk of progression and severe consequences of renal pathology, a preventive therapy as well as correction of kidney dysfunction are issues of a great importance today. An essential condition for an improvement of nephroprotection is a determination of new mechanisms of disturbances and restoration of homeostatic kidney processes. A unique physiological role of ATP-dependent potassium (KATP) channels and their participation in adaptive-compensatory reactions substantiate the feasibility of search for effective nephroprotectors among pharmacological modulators of their activity. The goal of research - to generalize available scientific data concerning the influence of KATP channels activators on kidneys for prospective administration of these pharmacological class representatives in nephroprotection. Analysis of renal effects of KATP channels activators allows stating a fact of perspectivity of the further studies of these pharmacological class representatives as the potential nephroprotectors in glomerular and tubular damage of the nephron.

NICORANDIL EFFICACY IN THE TREATMENT OF ISCHEMIC HEART DISEASE (REVIEW).

Nicorandil is an antianginal agent with a dual mechanism of action. It belongs to ATP-senitive potassium channel openers which has the beneficial effect in angina pectoris, playing an significant role in the dilation of arteries, veins and coronary artery. It leads to the relaxation of vascular smooth muscle and causes vasodilatation of major epicardial vessels. This effect is crucial for reducing risks of further damage in cases when percutaneous coronary intervention (PCI) is necessary. Relevant new studies concluded that Nicorandil has antiarrhythmic and cardioprotective effects by improving reperfusion, ultimately leading to a reduction in microvascular damage caused by PCI. Furthermore, Nicorandil addition to the standard therapy of paitents with ischemic heart disease has demonstrated improved quality of life.

[The efficacy of ivabradine in chronic heart failure (review)].

This review article is devoted to the treatment of chronic heart failure (HF) with a new generation drug - ivabradine. It is well known that HF is one of the most frequent reason of high mortality worldwide. HF is characterised by cardiac remodeling, which is central in the pathophysiology of HF including hemodynamic, neurohumoral and neurohormonal mechanisms during its development and established prognostic factor in patients suffered with this disease. Despite the introduction in medical practice of many drugs for the treatment of chronic HF the lethal outcome associated with HF remains high nowadays, which can be explained by complexity of remodeling mechanisms characteristic for development of HF. Ivabradine that has been introduced in medical practice in last decade is a pure heart rate-slowing agent. A large number of studies in patients with cardiovascular disease have demonstrated that heart rate (HR) is a very important and major independent risk factor for prognosis, because lowering of HR reduces cardiac work and diminished myocardial oxygen requirement. It was shown that ivabradine a selective inhibitor of the hyperpolarisation activated sodium chanel (If) is involved in pacemaker generation and responsiveness of the sino-atrial node resulting in HR reduction without negative inotropic action. Ivabradine in chronic HF improves diastolic function and attenuates cardiac tissue hypoxia. Long-term reduction of HR induced by ivabradine reduced remodeling and preserved nitric oxide (NO) bioavailability, resulting from processes triggered early after reduction of HR. The complex therapy including ivabradine promotes HR fall, leading in reduction of attacks of a stable angina and improved quality of life. Ivabradine may target the endothelial NO production via inhibition of protein tyrosine phosphatase 1B leading to endothelial protection. HR reduction by ivabradine reduces oxidative stress, improves endothelial function and prevents development of atherosclerostic changes in apolipoprotein E-deficient mice. In multicenter clinical trials it has been proved that ivabradine is superior to beta-blocking agents during complex therapy of chronic HF accompanied with its beneficial effects related to cardiac remodeling, improvement of the currency of HF and diminution of patients rehospitalisation. It is suggested that ivabradine as a newer agent is a valuable perspective drug for the treatment of congestive HF.