Targeting small arteries of hypertensive status with novel ATP-sensitive potassium channel openers.
The excessive contraction of small arteries under high blood pressure is the main contributor to the pathological change of hypertension. Current anti-hypertensive drugs, which lack a selective effect on small arteries in a hypertensive state, may cause many adverse effects. We have developed a novel opener of ATP-sensitive potassium channels, iptakalim, the vasorelaxing action of which is determined by the hypertensive status of small arteries. In conscious stroke-prone, spontaneously hypertensive rats and "two-kidneys, one-clip" renal hypertensive dogs, this compound produced long-lasting hypotensive effects, with no tolerance. Furthermore, it exerted a protective effect against hypertensive damage to target organs. Given its potency and fewer side effects, iptakalim hydrochloride is a promising drug for the treatment of hypertension.
Wang
Hai
H
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China. wh@nic.bmi.ac.cn.
Zhang
Ying-Li
YL
Chen
Yu-Ping
YP
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology*; D001158:Arteries / Q000187:drug effects* / Q000503:physiopathology*; D016503:Drug Delivery Systems; D004361:Drug Tolerance; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D015221:Potassium Channels / Q000819:agonists*
D000959:Antihypertensive Agents; D015221:Potassium Channels; D000255:Adenosine Triphosphate