Perivascular tissue of internal thoracic artery releases potent nitric oxide and prostacyclin-independent anticontractile factor

Objective: It has been recently suggested that perivascular tissue (PVT) releases hypothetic adipocyte- or adventitia-derived relaxing factor. The aim of the study was to assess anticontractile properties of perivascular tissue of human internal thoracic artery (ITA) and to check if this activity is nitric oxide (NO)- or proctacyclin-dependent. We also analyzed the influence of pleural adipose tissue on ITA reactivity. Methods: Human ITA rings were studied in vitro. First, skeletonized and pedicled ITA reactivity to serotonin and angiotensin 11 was compared. In subsequent experiments fragments of ITA were skeletonized and divided into two preparations. One was incubated alone, the other together with PVT or pleural adipose tissue floating freely in the bath. First, concentration-response curves to either serotonin or angiotensin 11 were constructed. Tissue was then transferred from one bath to the other and concentration-response curves were reconstructed. The same protocol was applied with the inhibition of NO synthase with L-NMMA ( 10(-4) M) and cyclooxygenase with indomethacin (10(-5) M). Results: Skeletonization augmented contractile response to serotonin (E-max 16.6 +/- 1.85 mN vs 43.8 +/- 3.87 mN; pedicled vs skeletonized ITA, respectively; p, < 0.001) and angiotensin II (E-max 10.9 +/- 1.07 mN vs 26.6 +/- 1.45 mN, respectively; p < 0.001). PVT presence in the bath caused decrease of E-max from 40.8 +/- 5.01 to 20.1 +/- 2.69 mN for serotonin; p < 0.001 and from 31.4 +/- 3.75 to 13.0 +/- 1.60 mN for angiotensin 11, p < 0.001 (PVT(-) vs PVT(+), respectively). PVT did not change ITA sensitivity (EC50) to serotonin or angiotensin II. Pleura[ adipose tissue did not change the contractile response of ITA to serotonin (E-max 37.2 +/- 4.95 mN vs 36.3 +/- 4.83 mN, pleural fat + and pleural fat-, respectively; p = 0.9). NO and prostacyclin inhibition failed to abolish anticontractile properties of perivascular tissue. PVT with cyclooxygenase and NO synthase inhibition decreased Em of serotonin from 46.6 +/- 3.03 to 28.2 +/- 4.02 mN, p < 0.001 and E-max of angiotensin II from 27.2 +/- 2.00 to 16.4 +/- 2.10 mN, p < 0.001. Conclusions: Perivascular tissue of ITA releases potent, soluble, nitric oxide and prostacyclin-independent anticontractile factor. The pleura( adipose tissue does not influence ITA reactivity to vasoconstrictors. Preservation of perivascular tissue may protect against vasospasm of ITA graft in clinical settings. (c) 2007 European Association for Cardio-Thoracic Surgery Published by Elsevier B.V. All rights reserved.