Angiotensin II increases nerve-evoked contractions in mouse tail artery by a T-type Ca(2+) 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 Ca(2+) 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 (0.1-1nM) 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 II on nerve-evoked contractions. Ang II increased vascular muscle reactivity to phenylephrine and UK-14304 (α1- and α2-adrenoceptor agonists, respectively). Endothelial denudation increased nerve-evoked contractions and reduced the facilitatory effect of Ang II on these responses. Efonidipine (L- and T-type Ca(2+) channel blocker) and NNC 55-0396 (T-type Ca(2+) channel blocker) also attenuated this effect of Ang II, while nifedipine (L-type Ca(2+) 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 Ca(2+) 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.