Apocynin reduces blood pressure and prevents development of endothelial dysfunction in SHR. Mechanisms underlying the effects of apocynin in SHR remain unclear. Angiotensin (Ang) II regulates NOX, the major source of ROS in cardiovascular system. We hypothesized that apocynin, acting as NOX inhibitor, may alter pressor and vasoconstrictor effects of Ang II in SHR. We analyzed the effect of Ang II on blood pressure, reactivity on aorta and mesenteric resistance arteries, plasmatic antioxidant capacity, NOX and NOS expression and activity, AT1 and AT2 receptors expression in blood vessels of SHR treated with apocynin SHR treated with apocynin (30 mg/Kg/day, p.o.). In SHR, apocynin reduced pressor effect of Ang II, increased plasmatic antioxidant capacity, ablated aortic and mesenteric NOX‐dependent ROS production, NOX2 and p47phox overexpression demonstrating that apocynin acts as a NOX inhibitor in blood vessels of SHR. Moreover, apocynin increased aortic and plasmatic nitrate/nitrite levels, but did not alter mesenteric NOS activity or eNOS expression, diminished AT1 expression in aortas and mesenteric bed, and increased AT2 expression in aortas from SHR. Apocynin increased endothelial modulation on Ang II vasoconstriction in resistance arteries from SHR. All these results demonstrated that in vivo treatment with apocynin induces important alterations of several mechanisms that lead to the reduction of the pressor and vasoconstrictor effects of Ang II in SHR. Apocynin effect involves further mechanisms besides the modulation of vascular ROS, which improve NO availability in vascular cells of SHR. These integrated data could help us to understand the promising effect of apocynin as an antihypertensive drug different from those currently used clinically.Support or Funding InformationApproved by local ethics committee CEUA FOA 450/2015.Financial support: CNPq, CAPES and FAPESP (2016/22180‐9).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.