Abstract-Pulse wave velocity (PWV), a direct marker of arterial stiffness, is an independent cardiovascular risk factor.Although the angiotensin II type 1 receptor blockade belongs to major antihypertensive and cardioprotective therapies, less is known about the effects of long-term stimulation of the angiotensin II type 2 receptor. Previously, compound 21, a selective nonpeptide angiotensin II type 2 receptor agonist improved the outcome of myocardial infarction in rats along with anti-inflammatory properties. We investigated whether compound 21 alone or in combination with angiotensin II type 1 receptor blockade by olmesartan medoxomil could prevent PWV increase and aortic remodeling in N -nitro-L-argininemethyl ester (L-NAME)-induced hypertension. Male adult Wistar rats (nϭ65) were randomly assigned to control, L-NAME, L-NAMEϩcompound-21, L-NAMEϩolmesartan, and L-NAMEϩolmesartanϩcompound-21 groups and treated for 6 weeks. We observed that L-NAME hypertension was accompanied by enhanced PWV, increased wall thickness, and stiffness of the aorta, along with elevated hydroxyproline concentration. Olmesartan completely prevented hypertension, PWV and wall thickness increase, and the increase of aortic stiffness and partly prevented hydroxyproline accumulation. Compound 21 partly prevented all of these alterations, yet without concomitant prevention of blood pressure rise. Although the combination therapy with olmesartan and compound 21 led to blood pressure levels, PWV, and wall thickness comparable to olmesartan-alone-treated rats, only in the combination group was complete prevention of increased hydroxyproline deposition achieved, resulting in even more pronounced stiffness reduction. We conclude that chronic angiotensin II type 2 receptor stimulation prevented aortic stiffening and collagen accumulation without preventing hypertension in rats with inhibited NO synthase. These effects were additive to angiotensin II type 1 receptor blockade, yet without additional blood pressurelowering effect, and they seem to be NO and blood pressure independent. Key Words: L-NAME Ⅲ vascular remodeling Ⅲ arterial stiffness Ⅲ pulse wave velocity Ⅲ renin-angiotensin system Ⅲ hypertension A rterial hypertension is a highly prevalent and still insufficiently controlled medical condition leading to severe cardiovascular complications. 1,2 One of the main contributors to the cardiovascular risk in these patients is the associated target organ damage. Augmented pulse wave velocity (PWV), which is considered to be the best and direct marker of arterial stiffness, 3 is regarded as an indicator of subclinical organ damage by current European guidelines for hypertension treatment. 4 The effects of current antihypertensive treatment on PWV have been investigated with various outcomes. The angiotensin II type 1 receptor (AT 1 R) antagonists, together with angiotensin-converting enzyme inhibitors, belong to the gold standard cardioprotective therapies. 5,6 In a study on 113 hypertensives, 2-to 3-year treatment with candesartan produced a l...

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Our results implicate Foxo3 in regulating NK cell function and suggest Foxo3 playing an important role in the antiviral innate immunity. Thus, enhanced FOXO3 activity such as in the polymorphism rs12212067 may be protective in chronic inflammation such as cancer and cardiovascular disease but disadvantageous to control acute viral infection.