Objective: We have studied the modulatory role of the adventitia on vascular tone and nitric oxide (NO) availability in response to noradrenaline (NA) and angiotensin II (Ang II).
Methods: Changes in isometric tension were determined in carotid arteries from 3-month-old Sprague-Dawley rats denuded from adventitia (-A) and compared to intact rings (+A). NO availability was assessed by the fluorescent NO indicator, 4,5-diaminofluorescein diacetate (DAF-2).
Results: Responses to NA (10(-10) to 10(-6) M) were: (i) significantly lower in -A compared to +A rings; (ii) equally enhanced in +A and -A rings without endothelium; and (iii) reduced in +A and -A rings incubated with superoxide dismutase (SOD; 15 U/ml). Responses to Ang II (10(-10) to 10(-7) M) were: (i) similar between +A and -A segments; (ii) equally reduced in both groups by SOD; and (iii) increased by endothelial denudation in both +A and -A arteries. Blockade of AT2 receptors with PD 123,319 (10(-7) M) significantly increased Ang II-induced contractions in +A rings. In segments preincubated with losartan (10(-5) M) and precontracted with NA (10(-7) M), Ang II elicited a relaxation that was abolished by l-NAME (10(-4) M), PD 123,319 (10(-7) M), and endothelium or adventitial removal. NO availability was increased in carotid rings stimulated with Ang II, but not with NA. This NO release was blocked by PD 123,319 (10(-7) M) and endothelium denudation.
Conclusions: These results suggest that the adventitia differently modulates responses to vasoconstrictors and that it is a key layer in Ang II-induced contractions, mediating NO release from the endothelium via AT2 receptors. This increase in NO counterbalances basal superoxide release.