VASOCONSTRICTOR RESPONSES TO POLYMORPHONUCLEAR LEUKOCYTES FROM ATHEROSCLEROTIC RABBITS

1. The vascular contractile effects of polymorphonuclear leucocytes (P MN) isolated from control rabbits and from rabbits made atheroscleroti c by 1% cholesterol feeding for 8 weeks were examined. 2. Rings of con trol rabbit thoracic aorta with or without endothelium were mounted at 2g tension in 10 mL organ baths and were submaximally contracted by p henylephrine (0.1 mu mol/L). After 30 min incubation at 37 degrees C, the supernatant of PMN (5 X 10(7)/mL, in Tyrode solution containing 0. 25% bovine serum albumin) was obtained by centrifugation for addition to the vascular preparation. 3. Control PMN supernatant (443 mu L) cau sed contraction (0.58+/-0.15g, n = 11) of phenylephrine-contracted aor tic rings, which was prevented by removal of the endothelium (0.11+/-0 .07 g, n = 5, P<0.05). However, the control PMN supernatant had no con tractile effect on aortic rings at resting tension (0.00+/-0.00g, n = 8). 4. By comparison, atherosclerotic PMN supernatant (443 mu L) cause d a significantly greater contraction of the aortic rings (1.41+/-0.13 g, n = 9, P<0.05 vs control PMN supernatant) that was only partly inhi bited by removal of the endothelium (0.45+/-0.20g, n = 9, P<0.05). Mor eover, PMN supernatants from four of seven atherosclerotic rabbits con tracted aortic rings at resting tension (3.5+/-1.4g, n = 7). 5. These results suggest that the release of a stable vasoconstrictor substance (s) by PMN is enhanced under conditions of atherosclerosis. The constr ictor action of this substance(s) appears to be greater in the presenc e of a functional endothelium, and part of its action may involve inac tivation of endothelium-derived nitric oxide.