Combination therapy based on the angiotensin receptor blocker olmesartan for vascular protection in spontaneously hypertensive rats

Abstract

For hypertension, combination therapies are recommended to achieve a low target blood pressure. In this study, the efficacy of combination therapies for preventing organ damage was investigated in spontaneously hypertensive rats (SHR). Twenty-week-old male SHR were orally administered olmesartan (Olm) (5 mg/kg/day) for the first 4 weeks. Subsequently, rats were randomly divided into 5 groups and administered add-on drugs for another 4 weeks as follows: Olm+Olm (5 mg/kg/day), Olm+azelnidipine (Aze) (30 mg/kg/day), Olm+temocapril (Tem) (10 mg/kg/day), Olm+atenolol (Ate) (5 mg/kg/day), Olm+hydrochlorothiazide (HCTZ) (5 mg/kg/day). Blood pressure and heart rate were measured at weeks 0, 4 and 8 by the tail-cuff method. Heart and kidney weights were determined, and endothelial function was assessed by evaluating the dilator response to acetylcholine. In comparison to untreated control SHR, a significant reduction in systolic blood pressure was observed at weeks 4 and 8 in all groups (p<0.05), while heart rate was significantly reduced at week 8 in only the Olm+Aze and Olm+Ate groups (p<0.05). In all groups, heart but not kidney weight was significantly decreased (p<0.05), and endothelial function was significantly improved (p<0.05) compared to the control SHR. In the Olm+Olm, Olm+Tem and Olm+Aze groups, endothelial function was significantly improved as compared to the other treatment groups (p<0.05). Thus, when using an angiotensin receptor blocker as a first-line therapy, an antihypertensive in the form of an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, or calcium channel blocker, such as azelnidipine, should be used as a second-line drug to protect against vascular damage.