[Hypoxic pulmonary hypertension and novel ATP-sensitive potassium channel opener: the new hope on the horizon].

Abstract

Hypoxic pulmonary hypertension (HPH) is a syndrome characterized by the increase of pulmonary vascular tone and the structural remodeling of peripheral pulmonary arteries. The aim of specific therapies for hypoxic pulmonary hypertension is to reduce pulmonary vascular resistance, reverse pulmonary vascular remodeling, and thereby improving right ventricular function. Iptakalim, a lipophilic para-amino compound with a low molecular weight, has been demonstrated to be a new selective ATP-sensitive potassium (K(ATP)) channel opener via pharmacological, electrophysiological, biochemical studies, and receptor binding tests. In hypoxia-induced animal models, iptakalim decreases the elevated mean pressure in pulmonary arteries, and attenuates remodeling in the right ventricle, pulmonary arteries and airways. Furthermore, iptakalim has selective antihypertensive effects, selective vasorelaxation effects on smaller arteries, and protective effects on endothelial cells, but no effects on the central nervous, respiratory, digestive or endocrine systems at therapeutic dose. Our previous studies demonstrated that iptakalim inhibited the effects of endothelin-1, reduced the intracellular calcium concentration and inhibited the proliferation of pulmonary artery smooth muscle cells. Since iptakalim has been shown safe and effective in both experimental animal models and phase I clinical trials, it can be a potential candidate of HPH in the future.

• Authors: Yu Jin, Wei-Ping Xie, Hong Wang
• Journal: Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology (Zhongguo Ying Yong Sheng Li Xue Za Zhi) Vol. 28 Issue 6 Pg. 510-23 (Nov 2012) ISSN: 1000-6834 [Print] China
• PMID: 23581180 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Endothelin-1
• KATP Channels
• N-(1-methylethyl)-1,1,2-trimethylpropylamine
• Propylamines
• Calcium

Topics

• Animals
• Antihypertensive Agents (therapeutic use)
• Calcium (metabolism)
• Disease Models, Animal
• Endothelin-1 (metabolism)
• Hypertension, Pulmonary (drug therapy)
• Hypoxia (drug therapy)
• KATP Channels (drug effects)
• Myocytes, Smooth Muscle (cytology, drug effects)
• Propylamines (therapeutic use)
• Pulmonary Artery (drug effects)