title: Mechanisms of improved aortic stiffness by arotinolol in spontaneously hypertensive rats.
abstract: OBJECTIVE
  This study investigates the effects on aortic stiffness and vasodilation by arotinolol and the underlying mechanisms in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  The vasodilations of rat aortas, renal and mesenteric arteries were evaluated by isometric force recording. Nitric oxide (NO) was measured in human aortic endothelial cells (HAECs) by fluorescent probes. Sixteen-week old SHRs were treated with metoprolol (200 mg·kg-1·d⁻¹), arotinolol (30 mg·kg-1·d⁻¹) for 8 weeks. Central arterial pressure (CAP) and pulse wave velocity (PWV) were evaluated via catheter pressure transducers. Collagen was assessed by immunohistochemistry and biochemistry assay, while endothelial nitric oxide synthase (eNOS) and eNOS phosphorylation (p-eNOS) of HAECs or aortas were analyzed by western blotting.
  
  
  RESULTS
  Arotinolol relaxed vascular rings and the relaxations were attenuated by Nω-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and the absence of endothelium. Furthermore, arotinolol-induced relaxations were attenuated by 4-aminopyridine (4-AP, Kv channels blocker). Arotinolol produced more nitric oxide compared to metoprolol and increased the expression of p-eNOS in HAECs. These results indicated that arotinolol-induced vasodilation involves endothelium-derived NO and Kv channels. The treatement with arotinolol in 8 weeks, but not metoprolol, markedly decreased CAP and PWV. Biochemistry assay and immunohistochemistry showed that aortic collagen depositions in the arotinolol groups were reduced compared with SHRs with metoprolol. Moreover, eNOS phosphorylation was significantly increased in aortinolol-treated SHR compared with SHRs with metoprolol.
  
  
  CONCLUSIONS
  Arotinolol improves arterial stiffness in SHR, which involved in increasing NO and decreasing collagen contents in large arteries.
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Wugang
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Mona
authors.initials: M
authors.lastname: Hong
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Dongrui
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Dingliang
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Hypertension, RuiJin Hospital, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors.forename: Pingjin
authors.initials: P
authors.lastname: Gao
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D008790:Metoprolol / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D059289:Vascular Stiffness / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015221:Potassium Channels; D011412:Propanolamines; D009569:Nitric Oxide; C024523:arotinolol; D003094:Collagen; D052250:Nitric Oxide Synthase Type III; D008790:Metoprolol