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) |
|---|---|
| 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 |
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Keywords
- Antihypertensives
- Ca-activated K channels
- EDHF
- Hypertension
- KCa2.3
- KCa3.1
- Restenosis
ASJC Scopus subject areas
- Drug Discovery
- Pharmacology
- Clinical Biochemistry
- Molecular Medicine
Cite this
Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease. / Köhler, Ralf; Kaistha, Brajesh P.; Wulff, Heike.
In: Expert Opinion on Therapeutic Targets, Vol. 14, No. 2, 02.2010, p. 143-155.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vascular KCa-channels as therapeutic targets in hypertension and restenosis disease
AU - Köhler, Ralf
AU - Kaistha, Brajesh P.
AU - Wulff, Heike
PY - 2010/2
Y1 - 2010/2
N2 - 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.
AB - 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.
KW - Antihypertensives
KW - Ca-activated K channels
KW - EDHF
KW - Hypertension
KW - KCa2.3
KW - KCa3.1
KW - Restenosis
UR - http://www.scopus.com/inward/record.url?scp=74949130493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=74949130493&partnerID=8YFLogxK
U2 - 10.1517/14728220903540257
DO - 10.1517/14728220903540257
M3 - Article
VL - 14
SP - 143
EP - 155
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
SN - 1472-8222
IS - 2
ER -