thromboxane-a2 and Hypothyroidism

Hypothyroidism induces a number of cardiovascular adaptations in rats, including decreases in blood flow to high-oxidative skeletal muscle and increases in total peripheral resistance. Conversely, exercise training results in elevations in blood flow to high-oxidative skeletal muscle and decreases in vascular resistance. The purpose of this study was to determine whether hypothyroidism induces changes in the vasomotor responses of arterial vessels and whether exercise training modifies these responses. Rats were divided into three groups, sedentary euthyroid (S-Eut), sedentary hypothyroid (S-Hypo), and exercise-trained hypothyroid (ET-Hypo). Responses to vasoactive compounds were examined in vitro using abdominal aortic rings. Maximal isometric contractile tension (g/mm2) evoked by KCl and norepinephrine (NE) were not different among groups. However, sensitivity to KCl [agonist concentration producing 50% of maximal vasoconstrictor response (EC50; in mM): S-Eut, 21.1 +/- 1.1; S-Hypo, 35.7 +/- 2.7; ET-Hypo, 43.8 +/- 2.0] and to NE [EC50 (in M): S-Eut, 4.0 x 10(-8) +/- 2.3 x 10(-8); S-Hypo, 8.3 x 10(-8) +/- 3.4 x 10(-8); ET-Hypo, 3.6 x 10(-7) +/- 1.1 x 10(-7)] was different among groups, and in the order S-Eut > S-Hypo > ET-Hypo. Maximal vasodilator responses induced by acetylcholine (10(-7) M NE preconstriction) were lower in rings from S-Hypo animals than those from S-Eut and ET-Hypo rats. Dilatory responses induced by sodium nitroprusside (SNP) with the same NE preconstriction were not different among groups. However, with a 10(-4) M NE preconstriction, maximal dilatory responses induced by SNP were lower in vessels from hypothyroid animals. Dilatory responses to forskolin (10(-4) M NE preconstriction) were not different among groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Aorta; Citrate (si)-Synthase; Hypothyroidism; Male; Muscles; Nitric Oxide; Nitroprusside; Physical Conditioning, Animal; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Sprague-Dawley; Thromboxane A2; Vasoconstrictor Agents; Vasodilator Agents; Vasomotor System

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)

Topics: 6-Ketoprostaglandin F1 alpha; Aging; Animals; Aorta; Arteries; Cholesterol; Hypothyroidism; Kinetics; Male; Rats; Thromboxane A2; Thromboxane B2; Thyroxine