Interleukin 10 limits increased blood pressure and vascular RhoA/Rho‐kinase signaling in angiotensin II‐infused mice

Interleukin‐10 (IL‐10) is a multi‐functional cytokine with potent anti‐inflammatory properties. We hypothesized that IL‐10 limits increased RhoA/Rho‐kinase signaling and vascular reactivity in arteries from angiotensin II (AngII) hypertensive rats. Wild‐type (WT) and IL‐10 knockout (−/−) mice were infused with AngII (90ng/min) for 14 days. WT mice infused or not with AngII, were treated with IL‐10 (0.4ng/min, 14 days) or dexamethasone (1.5mg/L, 14 days). Aortic rings were mounted in a myograph and concentration response curve to phenylephrine (PE) were evaluated. Blood pressure responses to AngII and maximal contraction to PE are greater in IL‐10 −/− mice, compared to WT (Fig.1). IL‐10 infusion, but not dexamethasone treatment, prevented the blood pressure increase in AngII WT mice (Fig.2). The augmented PE‐contraction observed in aorta from AngII WT mice was prevented by IL‐10 infusion and dexamethasone. Rho‐kinase inhibition (Y‐27632; 1μM) abolished differences in PE‐contraction and IL‐10 infusion or dexamethasone treatment seems to decrease Rho‐kinase activation in aorta from AngII WT. These studies demonstrate that IL‐10 counteracts both the pressoric activity of Ang II and vascular dysfunction associated with angiotensin II hypertension. Since the principal function of IL‐10 is to limit and terminate inflammatory responses, it may also provide a novel therapeutic target for the treatment of hypertension.