title: Beneficial effects of nebivolol and hydrochlorothiazide combination in spontaneously hypertensive rats.
abstract: OBJECTIVE
  This study examined the combined effect of nebivolol (NEB) and hydrochlorothiazide (HCTZ) on cardiovascular function in spontaneously hypertensive rats (SHR).
  
  
  METHODS
  SHR normotensive male rats were randomly assigned to five groups (n = 8 per group): (i) SHR control group; (ii) NEB 2 mg/kg per day group; (iii) HCTZ 10 mg/kg per day group; (iv) NEB 2 mg/kg per day + HCTZ 10 mg/kg per day group; (v) Eight age-matched Wistar-Kyoto normotensive male rats served as the control group. All groups were treated orally for 8 weeks.
  
  
  RESULTS
  The combination of NEB + HCTZ synergistically reduced systolic blood pressure and heart rate compared with either monotherapy. HCTZ increased water intake, which is a sign of diuresis. NEB reduced plasma angiotensin II concentration, which was increased in SHR and after HCTZ treatment. NEB + HCTZ increased plasma nitric oxide (NO) concentration and NO synthase activity, which were both reduced in SHR. NEB + HCTZ normalized femoral arterial vasorelaxation induced by acetylcholine, which was impaired in SHR.
  
  
  CONCLUSIONS
  The combination of NEB + HCTZ provided a number of beneficial and additive effects due to the synergistic characteristics of both drugs, in an experimental rat model of hypertension.
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Stefano
authors.initials: S
authors.lastname: Evangelista
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Zhang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004326:Drinking / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D000068577:Nebivolol; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine
keywords: Beta-blocker; diuretic; hydrochlorothiazide; hypertension; nebivolol; spontaneously hypertensive rats