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

Abstract

Abstract. For hypertension, combination therapies are recommended to acheive 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.

Total flavonoids from Plumula Nelumbinis suppress angiotensin II-induced fractalkine production by inhibiting the ROS/NF-κB pathway in human umbilical vein endothelial cells

“…Endothelial dysfunction is the foundation and initial step of numerous cardiovascular diseases, and promotes abnormal vascular growth, leading to end-organ damage (10,11). However, the underlying molecular mechanisms remain poorly understood.…”

A Low Fixed-dose Combination of Olmesartan and Azelnidipine Significantly Improves Endothelial Function in Uncontrolled Hypertension by Low Dose Amlodipine

“…6) In another report, this combination significantly ameliorated vascular endothelial function assessed by acetylcholine stimulation. 7) In human studies, 8) combination therapy with azelnidipine and olmesartan significantly improved aortic pulse wave velocity and Background: Flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NMD) in the brachial artery are well-known indices for evaluating endothelial function (ECF). The fixed-dose combination of olmesartan, an angiotensin receptor blocker (ARB, 10 mg), and azelnidipine (Ca-channel blocker; CCB, 8 mg: ARB-CCB) might effectively lower blood pressure in patients with uncontrolled hypertension and possibly ameliorate ECF.…”