title: Effect of ranolazine on rat intrarenal arteries in vitro.
abstract: Ranolazine is mainly used to treat patients with chronic stable angina in clinical practice. However, ranolazine does not lower significantly systemic blood pressure. The direct effect of ranolazine on vascular tone remains unknown. In the present study, we investigated the vascular effects and mechanisms of action of ranolazine in isolated rat intrarenal arteries. Rings of intrarenal arteries were mounted in a small vessel myography using two stainless steel wires for the measurement of isometric tension. L-type Ca²⁺ currents were recorded in isolated single renal arterial smooth muscle cells using patch clamp techniques in whole-cell mode. Ranolazine induced concentration-dependent relaxations in rings contracted with phenylephrine, but ranolazine failed to cause any relaxation in rings pre-contracted by U46619, 5-HT or endothelin-1. Ranolazine also induced relaxations in norepinephrine pre-contracted rings. Yohimbine failed to induce relaxation in rings pre-contracted by norepinephrine. Propranolol did not affect ranolazine-induced relaxation but the relaxant effect of ranolazine was much less than that of prazosin. Ranolazine-induced relaxations were slight but significantly attenuated by endothelial denudation. Partial inhibition was observed in endothelium-intact arteries exposed to a combination of iberiotoxin and apamin. Ranolazine at higher concentration (>30 μM) inhibited Ca²⁺-induced contraction in a noncompetitive manner. Ranolazine reduced L-type Ca²⁺ currents at potentials between -30 and 50 mV in isolated renal artery myocytes. Therefore it can be said that ranolazine has significant α₁-adrenergic receptor and weak calcium channel antagonistic effects in rat intrarenal arteries.
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, PR China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Deng
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Kuang
authors.forename: Fang
authors.initials: F
authors.lastname: Rao
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Xian-Hong
authors.initials: XH
authors.lastname: Fang
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Shan
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Li
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhou
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Wu
authors.forename: Xi-Yong
authors.initials: XY
authors.lastname: Yu
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Lin
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D058646:Adrenergic alpha-1 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009213:Myography; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology*; D000069458:Ranolazine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000083:Acetanilides; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010879:Piperazines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000069458:Ranolazine