Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease

Importance of the field. Cardiovascular disease is a leading cause of death in modern societies. Hyperpolarizing Ca2+-activated K+ channels (K-Ca) are important membrane proteins in the control of arterial tone and pathological vascular remodelling and thus could serve as new drug targets. Areas covered in this review. We summarize recent advances in the field of vascular K-Ca and their roles in cardiovascular pathologies such as hypertension and restenosis disease and draw attention to novel small-molecule channel modulators and their possible therapeutic utility. This review focuses on literature from the last four to five years. What the reader will gain: Pharmacological opening of endothelial K(Ca)3.1/K(Ca)2.3 channels stimulates endothelium-derived-hyperpolarizing-factor-mediated arteriolar dilation and lowers blood pressure. Inhibition of smooth muscle K(Ca)3.1 channels has beneficial effects in restenosis disease and atherosclerosis. We consider the therapeutic potential of K(Ca)3.1/KCa2.3 openers as novel endothelium-specific anti hypertensive drugs as well as of K(Ca)3.1 blockers for the treatment of pathological vascular remodelling and discuss advantages and disadvantages of the pharmacotherapeutic approaches Take home message: Pharmacological manipulation of vascular K-Ca channels by novel small-molecule modulators offers new venues for alternative treatments of hypertension, restenosis and atherosclerosis. Additional efforts are required to optimize these compounds and to validate them as cardiovascular-protective drugs.