Mechanisms of impaired vascular response to ANG II in perivascular injured carotid arteries of ovariectomized rat.

The rabbit carotid artery, injured by silicone collar, presents a perivascular inflammatory response and alterations in vascular responsiveness. Considering that angiotensin II (Ang II) plays an important role in cardiovascular physiology and pathology and that cardiovascular disease increases in postmenopausal women, the aim of this study was to investigate whether the Ang II contractile response in ovariectomized rat carotid artery is modified after a vascular injury by silicone collar. The positioning of the silicone collar around the common carotid artery for 14 days leads to an increased cross-sectional area of adventitial layer with inflammatory cells and an extensive angiogenesis. The Ang II-induced contraction was significantly decreased in collared arteries when compared with contralateral arteries. The reduction in the constrictor effect of Ang II in collared arteries was not modified by the presence of indomethacin (a non-selective inhibitor of cyclooxygenase) or PD 123,319 (a selective antagonist of the Ang II AT2 receptor). Moreover, while endothelium removal induced an increase in the Ang II responsiveness of both arteries (collared and contralateral), the Emax induced by Ang II was still lower in collared arteries. However, the "in vitro" pretreatment of the arteries with an inhibitor of nitric oxide synthase enzyme (L-NAME) significantly enhanced the maximal contractions response to Ang II only in injured arteries. Furthermore, the expression of iNOS (inducible nitric oxide synthase) was observed in the adventitial layer of collared arteries, indicating that the NO formed in the adventitial layer has an important role in injured arteries. Moreover, our data show impairment of extracellular calcium mobilization, mediated by Ang II, in the collared artery, although the intracellular calcium mobilization was not modified by the injury. In conclusion, the increased production of NO and a decrease in the calcium influx displayed by Ang II in the collared artery appears to counteract and reduce the biologic effect of Ang II.