title: Amlodipine ameliorates endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats.
abstract: 1. Endothelial dysfunction plays a critical role in the development and progression or pathogenesis of hypertension. Amlodipine, a calcium channel blocker, is an effective antihypertensive agent. We investigated the effects of amlodipine on endothelial dysfunction in mesenteric arteries from spontaneously hypertensive rats (SHR). 2. Eight-week-old SHR were treated with amlodipine (10 mg/kg per day) for 8 weeks. Control SHR and Wistar-Kyoto (WKY) rats were treated with saline. Systolic blood pressure (SBP) was measured by the tail-cuff method. Isometric tension changes of isolated mesenteric arterial rings were recorded continuously by a myograph system. Serum contents of malondialdehyde (MDA) and total nitrate/nitrite (NO(x) ) were determined. Vascular superoxide anion production was analysed with dihydroethidium (DHE) fluorescence. 3. The contractile responses to KCl and phenylephrine were greater in untreated SHR than in WKY. Acetylcholine (ACh)-induced relaxation was significantly impaired in untreated SHR. Amlodipine treatment reduced the contractions and improved relaxation to ACh. In WKY, relaxation to ACh was inhibited by N(G) -nitro-l-arginine methyl ester (l-NAME) and not changed by ascorbic acid. In untreated SHR, the response to ACh was unaffected by l-NAME, whereas it was improved by ascorbic acid. Amlodipine restored the inhibitory effect of l-NAME on ACh-induced relaxation, but ascorbic acid no longer exerted its facilitating effect. Amlodipine prevented the rise in SBP and ameliorated abnormalities in serum MDA and NO in untreated SHR. DHE assay showed an increased intravascular superoxide generation in untreated SHR, which was abrogated by amlodipine. 4. Treatment of SHR with amlodipine resulted in amelioration of endothelial dysfunction by anti-oxidant activity and improvement in NO availability.
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University, College of Medicine, Xi'an, China.
authors.forename: Xi
authors.initials: X
authors.lastname: He
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Jun-Lu
authors.initials: JL
authors.lastname: Yang
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Li
authors.forename: Hong-Ke
authors.initials: HK
authors.lastname: Jiang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Yu
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D009609:Nitrous Oxide / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D013481:Superoxides; D017311:Amlodipine; D010656:Phenylephrine; D008315:Malondialdehyde; D011189:Potassium Chloride; D009609:Nitrous Oxide; D000109:Acetylcholine; D001205:Ascorbic Acid; D019331:NG-Nitroarginine Methyl Ester