Mechanisms of vasodilatatory effect of perivascular tissue of human internal thoracic artery.

It has beed showed that perivascular adipose tissue (PVAT) of human internal thoracic artery (ITA) releases adventitia/adipocyte-derived relaxing factor (ADRF). The precise mechanism of vasodilatatory effect of ADRF is still unknown. It was suggested that various potassium channels may be involved in the action of ADRF. The aim of this study was to assess the involvment of potassium channels in the vasorelaxing properties of ADRF in human internal thoracic artery. Human ITA rings were studied in vitro. First the ability of perivascular tissue of human ITA to release ADRF to the bath was checked. In subsequent experiments two fragments of skeletonised ITA were used to assess the involvement of various potassium channels in vasorelaxing action of PVAT. Segment of ITA, precontracted with serotonin (10(-5.5)M), was relaxed by adding PVAT to tissue bath, first without and then in the presence of appropriate potassium channel blocker. Second segment served as a control (no addition of PVAT). The magnitude of relaxation was measured and compared between preparations. This protocol was used to analyze the influence of iberiotoxin (100 nM), apamin (1 uM), 4-aminopyridine (1 mM, 5 mM), BaCl₂ (100 uM) and glibenclamide (10 uM). The addition of PVAT to precontracted skeletonized ITA caused significant vasorelaxation (54.6±8.03 mN versus 33.7±6.58 mN p=0.03). Similar effect was seen when 5 ml of aliquot from separate incubation of PVAT was added (36.3±5.45 mN versus 20.7±3.02 mN; p<0.001). PVAT dependent relaxation was blocked in the presence of Ca⁺² dependent potassium channel blocker iberiotoxin (47.4±16.67 mN versus 43.3±14.54 mN; p=0.36) and 4-aminopyridine (5 mM) (59.3±3.54 mN versus 51.6±4.77 mN; p=0.12). We conclude that perivascular adipose tissue of human ITA releases relaxing factor that seems to act with the involvement of Ca⁺² dependent potassium channels.