Thrombin-induced endothelium-dependent relaxation and its inhibition by LDL in porcine coronary arteries.

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Abstract
The effects of thrombin on the vascular tone of porcine coronary arteries and the influence of LDL on the thrombin effects were investigated. A segment of porcine coronary arteries was mounted under 1.5g resting tension to measure the isometric force. LDL was prepared from porcine serum by ultracentrifugation and dialysis against Tyrode buffer. Thrombin (0.1-0.3 U/ml) dose-dependently relaxed intact porcine coronary arteries precontracted with PGF 2a (10-5M). The removal of the endothelium by rubbing abolished the thrombin effect. This relaxation was also abolished by methylene blue (10-5M), but was unaffected by indomethacin (5×10-5M). At these concentrations, thrombin per se exerted a slight contractile effect on the resting tension of the coronary arteries with or without the endothelium. An addition of LDL (1 mg protein/ml) to the solution did not affect the precontraction of PGF 2a. However, LDL dose-dependently hibited the thrombin-induced relaxation of coronary arteries precontracted with PGF 2a. Albumin (1 mg protein/ml) lacked such effects. Relaxation by sodium nitroprusside (10-6M) was unaffected by the LDLtreatment. These results suggest that LDL, a major atherogenic factor, directly influences the endothelium-dependent vasodilation by thrombin in the coronary arteries.