Effects of hypothyroidism and short-term aging on whole blood thromboxane and arterial prostacyclin synthesis.
Hypothyroidism results in decreased platelet aggregation and has unique effects on the development of atherosclerosis and angina pectoris. Because prostacyclin and thromboxane A2 profoundly influence platelet function and vascular tone and are thought to be important in the development of atherosclerosis and angina pectoris, we studied the effects of hypothyroidism in rats on the in vitro elaboration of prostacyclin passively by aortic tissue and of thromboxane A2 by thrombin-stimulated whole blood. Hypothyroidism induced by iodine 131 (given at age 7 weeks) persistently caused a mild decrease in platelet count (P less than 0.01) and 30% decrease in immunoreactive thromboxane B2 (the hydrolysis product of thromboxane A2) generation per platelet (P less than 0.01) compared with age-matched euthyroid rats. Between 20 and 23 weeks of age immunoreactive 6-ketoprostaglandin F1 alpha (the hydrolysis product of prostacyclin) generation decreased by 30% in euthyroid rats. In hypothyroid rats less than 23 weeks of age, 6-ketoprostaglandin F1 alpha production was the same as that of age-matched euthyroid rats. With further aging, 6-ketoprostaglandin F1 alpha production did not decrease as it did in euthyroid rats. Hypothyroid rats more than 20 weeks old had, therefore, significantly greater 6-ketoprostaglandin F1 alpha production than age-matched euthyroid rats (P less than 0.005). L-Thyroxine given daily for 28 days to 23-week-old hypothyroid rats caused a rapid increase in platelet count and a delayed normalization of the thromboxane synthetic abnormality. 6-Ketoprostaglandin F1 alpha production transiently increased in response to L-thyroxine, but decreased to the euthyroid level after 28 days of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Sjoberg
R J
RJ
Department of Medicine, Fitzsimons Army Medical Center, Aurora, CO 80045-5001.
Kidd
G S
GS
Swanson
E W
EW
O'Barr
T P
TP
Corby
D G
DG
Hofeldt
F D
FD
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D013928:Thromboxane A2 / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D002784:Cholesterol; D013974:Thyroxine