Angiotensin II increases nerve-evoked contractions in mouse tail artery by a T-type Ca2+ channel-dependent mechanism

Angiotensin II (Ang II) increases sympathetic nerve-evoked contractions of arterial vessels. Here the mechanisms underlying this effect were investigated in mouse tail artery. Isometrically mounted segments of mouse distal tail artery were used to investigate the effects of endothelium denudation, blocking Ca2+ channels and inhibiting superoxide signalling on Ang II-induced facilitation of nerve-evoked contractions. In addition, in situ amperometry was used to assess effects of Ang II on noradrenaline release. Ang II (0.1-1 nM) increased nerve-evoked contractions but did not change noradrenaline release. Losartan (Ang II type 1 receptor antagonist), but not PD 123319 (Ang II type 2 receptor antagonist), blocked the facilitatory effect of Ang lIon nerve-evoked contractions. Ang II increased vascular muscle reactivity to phenylephrine and UK-14304 (alpha(1)- and alpha 2-adrenoceptor agonists, respectively). Endothelial denudation increased nerve-evoked contractions and reduced the facilitatory effect of Ang II on these responses. Efoniclipine (L- and T-type Ca2+ channel blocker) and NNC 55-0396 (T-type Ca2+ channel blocker) also attenuated this effect of Ang II, while nifeclipine (L-type Ca2+ channel blocker) did not Blockers of superoxide generation/signalling did not change the facilitatory effect of Ang II on nerve-evoked contractions. The findings indicate that Ang II increases the contribution of T-type Ca2+ channels to neural activation of the vascular muscle. In addition, Ang II appears to reduce the inhibitory influence of the endothelium on nerve-evoked contractions. (C) 2015 Elsevier B.V. All rights reserved.