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Targeting hypertension with a new adenosine triphosphate-sensitive potassium channel opener iptakalim.
J Cardiovasc Pharmacol. 2010 Sep; 56(3):215-28.JC

Abstract

Hypertension is the most common cardiovascular disease. The discovery of the antihypertensive action of adenosine triphosphate-sensitive potassium (K(ATP)) channel openers was a significant advance in the treatment of hypertension. Iptakalim is a novel K(ATP) channel opener with a unique chemical structure that differs from other K(ATP) openers. Among the 3 different subtypes of K(ATP) channels heterologously expressed in human embryonic kidney cells and Xenopus oocytes, iptakalim exhibits significant selectivity for SUR2B/Kir6.1 channels, mild effects on SUR2A/Kir6.2 channels, and fails to open SUR1/Kir6.2 channels. Iptakalim is a more potent activator of the SUR2B/Kir6.1 subtype of K(ATP) channels than diazoxide and pinacidil, the 2 most commonly studied K(ATP) channel openers. Iptakalim selectively produces arteriolar vasodilation with essentially no effect on the capacitance vessels. It can preferentially relax arterioles and small arteries, without affecting large arteries. Furthermore, iptakalim strongly lowers the blood pressure of hypertensive rodents and humans but has little effect on normotensive rodents and humans. Selective antihypertensive action is not observed with pinacidil or diazoxide and may be due to the high selectivity of iptakalim for the SUR2B/Kir6.1 subtype of K(ATP) channels, as well as its selective relaxation of resistance vessels. In pulmonary arterial smooth muscle cells, iptakalim inhibits the increase of cytoplasmic free Ca2+ concentration, as well as cell proliferation induced by endothelin-1. Furthermore, iptakalim has exerted protective effects against hypertensive damage to target organs in rats and improves endothelial dysfunction associated with cardiovascular diseases by selective activation of the SUR2B/Kir6.1 subtype of K(ATP) channels expressed in the endothelium. Clinical trials of iptakalim in the treatment of mild-moderate hypertension have been completed in China. In additional to strong antihypertensive efficacy, iptakalim seems to have a favorable safety and tolerability profile. Iptakalim is a promising new generation antihypertensive drug.

Authors+Show Affiliations

Department of Cardiovascular Pharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20410832

Citation

Pan, ZhiYuan, et al. "Targeting Hypertension With a New Adenosine Triphosphate-sensitive Potassium Channel Opener Iptakalim." Journal of Cardiovascular Pharmacology, vol. 56, no. 3, 2010, pp. 215-28.
Pan Z, Huang J, Cui W, et al. Targeting hypertension with a new adenosine triphosphate-sensitive potassium channel opener iptakalim. J Cardiovasc Pharmacol. 2010;56(3):215-28.
Pan, Z., Huang, J., Cui, W., Long, C., Zhang, Y., & Wang, H. (2010). Targeting hypertension with a new adenosine triphosphate-sensitive potassium channel opener iptakalim. Journal of Cardiovascular Pharmacology, 56(3), 215-28. https://doi.org/10.1097/FJC.0b013e3181e23e2b
Pan Z, et al. Targeting Hypertension With a New Adenosine Triphosphate-sensitive Potassium Channel Opener Iptakalim. J Cardiovasc Pharmacol. 2010;56(3):215-28. PubMed PMID: 20410832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting hypertension with a new adenosine triphosphate-sensitive potassium channel opener iptakalim. AU - Pan,ZhiYuan, AU - Huang,JingHui, AU - Cui,WenYu, AU - Long,ChaoLiang, AU - Zhang,YanFang, AU - Wang,Hai, PY - 2010/4/23/entrez PY - 2010/4/23/pubmed PY - 2011/2/15/medline SP - 215 EP - 28 JF - Journal of cardiovascular pharmacology JO - J Cardiovasc Pharmacol VL - 56 IS - 3 N2 - Hypertension is the most common cardiovascular disease. The discovery of the antihypertensive action of adenosine triphosphate-sensitive potassium (K(ATP)) channel openers was a significant advance in the treatment of hypertension. Iptakalim is a novel K(ATP) channel opener with a unique chemical structure that differs from other K(ATP) openers. Among the 3 different subtypes of K(ATP) channels heterologously expressed in human embryonic kidney cells and Xenopus oocytes, iptakalim exhibits significant selectivity for SUR2B/Kir6.1 channels, mild effects on SUR2A/Kir6.2 channels, and fails to open SUR1/Kir6.2 channels. Iptakalim is a more potent activator of the SUR2B/Kir6.1 subtype of K(ATP) channels than diazoxide and pinacidil, the 2 most commonly studied K(ATP) channel openers. Iptakalim selectively produces arteriolar vasodilation with essentially no effect on the capacitance vessels. It can preferentially relax arterioles and small arteries, without affecting large arteries. Furthermore, iptakalim strongly lowers the blood pressure of hypertensive rodents and humans but has little effect on normotensive rodents and humans. Selective antihypertensive action is not observed with pinacidil or diazoxide and may be due to the high selectivity of iptakalim for the SUR2B/Kir6.1 subtype of K(ATP) channels, as well as its selective relaxation of resistance vessels. In pulmonary arterial smooth muscle cells, iptakalim inhibits the increase of cytoplasmic free Ca2+ concentration, as well as cell proliferation induced by endothelin-1. Furthermore, iptakalim has exerted protective effects against hypertensive damage to target organs in rats and improves endothelial dysfunction associated with cardiovascular diseases by selective activation of the SUR2B/Kir6.1 subtype of K(ATP) channels expressed in the endothelium. Clinical trials of iptakalim in the treatment of mild-moderate hypertension have been completed in China. In additional to strong antihypertensive efficacy, iptakalim seems to have a favorable safety and tolerability profile. Iptakalim is a promising new generation antihypertensive drug. SN - 1533-4023 UR - https://www.unboundmedicine.com/medline/citation/20410832/Targeting_hypertension_with_a_new_adenosine_triphosphate_sensitive_potassium_channel_opener_iptakalim_ L2 - https://doi.org/10.1097/FJC.0b013e3181e23e2b DB - PRIME DP - Unbound Medicine ER -