title: Nipradilol inhibits atmospheric pressure-induced cell proliferation in human aortic smooth muscle cells.
abstract: Hypertension is a major risk factor for atherosclerosis and the genesis of cardiovascular and cerebrovascular diseases. Therefore, the protection of atherosclerosis progression is one of the purpose of an anti-hypertensive treatment in vascular system. Nitric oxide (NO)-releasing drugs have been reported to have an inhibitory effect on shear stress-induced extracellular signal-regulated kinase (ERK) activation in endothelial cells. For further understanding of the effects of these drugs, the present study focused on the effects on intracellular signal transduction and cell proliferation in cultured human aortic smooth muscle cells (HASMC) under high atmospheric pressure. Three hours of 160-mmHg atmospheric pressure resulted in an approximately 380% increase in cell proliferation compared to non-pressurized controls. Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylaminoproxy)-3-nitroxy-2H-1-benzopyran) (10(-6)M) demonstrated approximately 40% reduction in cell proliferation compared to that shown by pressurized HASMC as a vehicle control. Three hours of 160-mmHg atmospheric pressure resulted in a 25% increase in the amount of activated ERKs. Nipradilol (10(-6)M) demonstrated approximately a 26% reduction in the amount of activated ERKs. NO(x) concentration under the presence of nipradilol (10microM) with HASMC resulted in a 7.2microM of NO production and was 2.4-fold more than that from no dug control (3.0microM). An administration of L-NAME (10(-4)M) supplemented with Nipradilol (10(-6)M) did not show any significant effect on cell proliferation. From these observations, we concluded that nipradilol has an anti-proliferative effect on HASMC under high atmospheric pressure. Nipradilol may act as a nitric oxide inducer from HASMC and suspected to work as a supplement to mitigate the impaired endothelial cell function caused by hypertension.
authors.affiliation: Department of Laboratory Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. kiizuka@med.hokudai.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Iizuka
authors.forename: Noriteru
authors.initials: N
authors.lastname: Morita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murakami
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kawaguchi
mesh_terms: D001011:Aorta / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D001274:Atmospheric Pressure; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology*
chemical_list: D006131:Growth Inhibitors; D011412:Propanolamines; C036089:nipradilol