19 - Apocynin reduces pressor and vasoconstrictor effects of Ang II in SHR

Abstract

NAD(P)H oxidase (NOX) activity and expression can be activated by angiotensin (Ang) II. We have previously observed that apocynin, a NOX inhibitor, prevented endotelial dysfunction and reduced blood pressure by increasing nitric oxide (NO) and reducing ROS concentrations in endothelial cells. We evaluated the effect of apocynin on the contractile responses to Ang II in resistance arteries of SHR and the mechanisms involved on these effects. SHR were treated from the 4th to the 10th week of life with apocynin (30 mg/Kg). Wistar rats were used as normotensive control. Using mesenteric arteries, we performed concentration-response curves to Ang II and determined eNOS and NOX isoforms and subunits expressions, lucigenin chemiluminescence and nitrate/nitrite levels. Data were expressed as mean ± SEM. Apocynin increased endothelium modulation and/or NOS activity on Ang II vasoconstrictor responses in mesenteric arteries of SHR. Treatment with apocynin did not alter NO synthase activity, and eNOS, NOX1, NOXO1, and NOX4 expressions, however, it decreased NOX2 and p47phox expressions in mesenteric beds of SHR treated. Moreover, treatment apocynin was able to decrease ROS production in these vessels. The lower reactivity of Ang II in resistance arteries would lead to lower peripheral vascular resistance and consequently the reduction of mean arterial pressure and Ang II pressor effect in SHR treated with apocynin, as previously observed. 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. Ethics Comittee CEUA FOA 450/2015. Financial Support FAPESP 2016/22180-9, CAPES and CNPq.