Beneficial effects of nebivolol and hydrochlorothiazide combination in spontaneously hypertensive rats. 
This study examined the combined effect of nebivolol (NEB) and hydrochlorothiazide (HCTZ) on cardiovascular function in spontaneously hypertensive rats (SHR).  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.  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.  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.