Pathological significance of the thromboxane-prostacyclin hypothesis.
Disturbances in the balance between the production of thromboxane A2 by the platelets and that of prostacyclin by the vessel wall may play a major role in disease and be a target for therapeutic agents. Acetylsalicylic acid, given in small doses, may inhibit the production of thromboxane A2 without affecting that of prostacyclin. Even if it reduces prostacyclin synthesis, the drug is beneficial as an antithrombotic agent, possibly because it has actions not related to inhibition of cyclooxygenase. Dazoxiben not only inhibits the production of thromboxane A2 by platelets, but also facilitates that of prostanoids, in part by diverting endoperoxides to the blood vessel wall and to leukocytes. Although reduced production of prostacyclin may contribute to the etiology of atherosclerosis, the blood vessel wall of hypercholesterolemic animals exhibits an increased production of prostacyclin. The latter has been given successfully in patients with accelerated turnover of platelets or with peripheral vascular disease. However, its very short t1/2 limits its practical use. The availability of stable prostacyclin derivates, such as ZK 36374, may bypass this problem.
R
R
Paoletti
P
P
Maderna
E
E
Tremoli
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000502:physiology*; D014652:Vascular Diseases / Q000188:drug therapy
D011465:Prostaglandins, Synthetic; D013931:Thromboxanes; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D001241:Aspirin