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.

Keywords:

• β-blocker
• diuretic
• hydrochlorothiazide
• nebivolol
• nitric oxide
• spontaneous hypertensive rats

Acknowledgements

The authors would like to thank ContentEdNet for English language assistance, Donatella Bemporad, for her advice and suggestions and Alessandro Pineda and Sabrina Cecili for their technical support.

Financial & competing interests disclosure

All authors are employees of Menarini Spa, part of the Menarini group, European marketing authorization holder of the combination nebivolol and hydrochlorothiazide. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.