The role of lysolecithin in the relaxation of vascular smooth muscle

The effect of lysolecithin (lysophosphatidylcholine) on the relaxation of rabbit aortic strip closely resembled that produced by acetylcholine (ACh) which releases the endothelium-derived relaxing factor (EDRF). Relaxation induced by lysolecithin depended on the presence of endothelium and was inhibited by hemoglobin and methylene blue. It appeared to be mediated by the second messenger, c-GMP. Lysolecithin induced relaxation was slower but more persistent than that resulting from the endothelium-derived relaxing factor (EDRF) produced by acetylcholine (ACh). Like lysolecithin, Triton X-100, a non-ionic detergent, also preferentially relaxed aortic strips with intact endothelium. The results demonstrate the importance of phospholipids derived from cell membranes in vascular smooth muscle relaxation. Endothelium-derived relaxing factors appear as a group of heterogeneous substances.

EFFECTS OF DEFIBROTIDE TREATMENT ON THE PLASMA AND SERUM INDUCED CONTRACTION OF RABBIT AORTIC STRIP IN RELATION TO THE PATHOPHYSIOLOGY OF MYOCARDIAL INFARCTION

Several clinical and experimental studies have demonstrated the efficacy of a polydeoxyribonucleotide (Defibrotide) in myocardial ischemic disorders and peripheral arterial diseases. In attempts to investigate the mechanisms of action of this agent, we used a modified rabbit model of hemodynamics and an isolated rabbit aortic strip preparation. Intravenous bolus administration of Defibrotide at 5-50 mg/kg did not produce any changes in the mean arterial blood pressure up to 3 hours. Defibrotide treated rabbits also resisted human serum-stasis and stasis alone induced venous and arterial thrombus formation. Serum and plasma from Defibrotide treated animals were tested for their direct contractile and procontractile (synergistic with an epinephrine stimulus) activities on rabbit aortic strips. In contrast to plasma and serum from saline treated rabbits, both serum and plasma produced relatively weak or no effects. The dose-contrac-tion responses were shifted to the right suggesting that serum from Defibrotide treated animals contained much lesser amounts of contractile substances. This data indicates blood from Defibrotide treated rabbits is compositionally different than normal, either due to lack of cellular product formation (thromboxane B 2, serotonin) or due to the generation of endothelial products which are inhibitory to the contractile effects of substances generated during the formation of a thrombus. Plasma thromboxane B2/6 keto-PGFia ratios were also found to be much higher in Defibrotide treated groups when compared to the saline groups. The observed therapeutic effect of Defibrotide in acute myocardial infarction may be linked with the inhibition of the formation of thrombus and with the mediation of vascular spasm due to the generation of inhibitory substances or the lack of generation of spasmogenic substances.