title: Combined antihypertensive and cardioprotective effects of nebivolol and hydrochlorothiazide in spontaneous hypertensive rats.
abstract: The antihypertensive and cardioprotective effects of the combination of nebivolol (NEB) and hydrochlorothiazide (HCTZ) in spontaneously hypertensive rats (SHR) were investigated. SHR and age-matched Wistar-Kyoto normotensive rats were randomly assigned to one of six groups: SHR treated with NEB (1 mg/kg/day, intragastric); SHR treated with HCTZ (5 mg/kg/day, intragastric); SHR treated with NEB plus HCTZ (1 + 2.5 mg/kg/day); SHR treated with NEB plus HCTZ (1 + 5 mg/kg/day), along with a SHR and a WKY control group. The effects of NEB and HCTZ on clinical chemistry parameters and on cardiac function and structure were evaluated. NEB and HCTZ in combination had synergistic antihypertensive effects and significantly reduced heart rate and blood pressure compared with monotherapy with either agent. These effects were independent of water intake, urine output and electrolyte excretion. NEB plus HCTZ was associated with reduced oxidative stress in terms of glutathione availability, lower angiotensin I levels as index of plasma renin activity and reduced clearance of urinary sodium compared with HCTZ alone. Cardiac morphometric data and antioxidant parameters indicate that NEB may influence cardiac structure by reducing hypertrophy and by enhancing the availability of endothelial nitric oxide - a unique characteristic of NEB. The authors suggest that a combination of NEB and HCTZ for the treatment of hypertension may be useful for the synergistic characteristics of both drugs.
authors: Menarini Ricerche SpA, Pharmacology Department, Via Tito Speri 10, 00040 Pomezia, Roma, Italy.
authors: Giuseppe
authors: G
authors: Sacco
authors: Stefano
authors: S
authors: Evangelista
authors: Stefano
authors: S
authors: Manzini
authors: Massimo
authors: M
authors: Parlani
authors: Mario
authors: M
authors: Bigioni
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000209:etiology / Q000517:prevention & control*; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D000068577:Nebivolol; D010975:Platelet Aggregation Inhibitors; D051381:Rats; D011921:Rats, Inbred WKY; D016896:Treatment Outcome
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004232:Diuretics; D004983:Ethanolamines; D010975:Platelet Aggregation Inhibitors; D000068577:Nebivolol; D006852:Hydrochlorothiazide