Beneficial effects of nebivolol and hydrochlorothiazide combination in spontaneously hypertensive rats

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.