[Endothelial mitochondria--a novel target for pharmacology of endothelial dysfunction]. / Mitochondria sródblonka--nowy cel dla farmakologii dysfunkcji sródblonka.

Vascular endothelium the inside layer of the cardiovascular system is presently looked upon as an important paracrine, autocrine and endocrine organ that determines the health of the cardiovascular system. In fact, healthy endothelium is essential for homeostasis of cardiovascular system, while endothelial dyfunction leads to cardiovascular diseases including atherosclerosis, diabetes and heart failure. Endothelial dysfunction is tightly linked to the overproduction of reactive oxygen species, development of oxidant stress and inflammatory response of endothelium. Mitochondria of the vascular endothelium seem to be an important player in these processes. In contrast to numerous cell types, synthesis of ATP in endothelium occurs in major part via a glycolytic pathway and endothelium seem to be relatively independent of the mitochondrial pathway of energy supply. However, as evident from recent studies, mitochondrial pathways of free radicals production tighly linked to mitochondrial and cytosol changes in the ion homeostasis play an important role in the regulation of endothelial inflammatory response, in the development of oxidative stress and apoptosis of vascular endothelium. Therefore, endothelial mitochondria appears critical in the regulation of endothelial functions and represent a novel target in pharmacology of endothelial dysfunction in cardiovascular diseases.

Endothelial mitochondria as a possible target for potassium channel modulators.

Variety of ion channels is present in plasma membrane of endothelial cells. These include the potassium channels such as Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels, voltage-dependent K(+) channels and also ATP-regulated K(+) channels. Due to an influence on the membrane potential they are important regulators of vascular tone by modulating endothelial calcium ions signaling and synthesis of vasodilating factors. Potassium channels in mitochondrial membranes of various tissues, similar to plasma membrane potassium channels, are described. Mitochondrial potassium channels such as ATP-regulated or large conductance Ca(2+)-activated and voltage gated channels are implicated in cytoprotective phenomenon in different tissues. In this paper we describe the pharmacological properties of mitochondrial potassium channels and discuss their role of as novel pharmacotherapeutic targets in endothelium.