Abstract
Importance of the field: Cardiovascular disease is a leading cause of death in modern societies. Hyperpolarizing Ca2+-activated K+ channels (KCa) 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 KCa 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 KCa3.1/ KCa2.3 channels stimulates endothelium-derived-hyperpolarizing-factormediated arteriolar dilation and lowers blood pressure. Inhibition of smooth muscle KCa3.1 channels has beneficial effects in restenosis disease and atherosclerosis. We consider the therapeutic potential of KCa3.1/KCa2.3 openers as novel endothelium-specific antihypertensive drugs as well as of KCa3.1- blockers for the treatment of pathological vascular remodelling and discuss advantages and disadvantages of the pharmacotherapeutic approaches. Take home message: Pharmacological manipulation of vascular KCa 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.
Original language | English (US) |
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Pages (from-to) | 143-155 |
Number of pages | 13 |
Journal | Expert Opinion on Therapeutic Targets |
Volume | 14 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2010 |
Keywords
- Antihypertensives
- Ca-activated K channels
- EDHF
- Hypertension
- KCa2.3
- KCa3.1
- Restenosis
ASJC Scopus subject areas
- Drug Discovery
- Pharmacology
- Clinical Biochemistry
- Molecular Medicine