Nova saznanja u farmakologiji endotelne disfunkcije

Abstract

Homeostasis of different blood vessels is directly linked with physiological and pathological features of morphological and functional integrity of vascular endothelial cells. Vascular endothelium has a central role in the modulation of vascular tone, together with established local antioxidant, anti-inflammatory, profibrinolytic, anti-adhesive and anticoagulant activity. These effects are results of timely production and release of vaso-active autacoids, where nitric oxide, prostacyclin and endothelially-derived hyperpolarizing factor are considered to be crucial for physiological cellular signaling mechanisms. In contrast, endothelial dysfunction is a pathological process, which is known to be correlated with different vascular pathological conditions. It is basically characterized by marked disturbance of the regulation of vascular tone, as a consequence of reduced bio-availability of endothelial relaxing factors and concomitant enhanced production of endothelial contractile factors. Moreover, endothelial cells are affected by oxidative stress and increased inflammatory processes that are all associated with migration of circulating leukocytes in subendothelial space and enhanced pathological proliferation of adjacent smooth muscle cells. Pharmacological approach in improving endothelial dysfunction currently represents a crucial part in different cardiovascular clinical trials. Conventional drugs, including statins, ACE-inhibitors, angiotensin receptor blockers, oral antidiabetic agents or some beta adrenoceptor antgonists, all have clearly established efficacy in improving endothelial function, either via direct or indirect mechanisms of action. Besides, it has been concluded that, under specific conditions, some dietary ingredients, natural products or specific dietary supplements can improve endothelial dysfunction and overall vascular homeostasis. Owing to the fact that endothelial dysfunction was confirmed to be associated with etiology and/or further progression of different vascular disturbances, clinical investigations of novel pharmacological possibilities for improving endothelial dysfunction still represents an up-to-date trend in scientifically-based attempts of discovering a viable therapeutic solutions in treating cardiovascular diseases.