A study of cardiac effects of thyroid hormones: evidence for amelioration of the effects of thyroxine by sodium ipodate.
We studied the effects of daily ip administration of T4 (200 micrograms/100 g BW) or T3 (50 micrograms/100 g) to the rat (six per group) for 3 days with or without sodium ipodate (6 mg/100 g), propylthiouracil (PTU; 2 mg/100 g), propranolol (0.5 mg/100 g), or amiodarone (2.5 mg/100 g) on cardiac weight, 3',5'-diiodothyronine (3',5'-T2) to 3'-monoiodothyronine monodeiodinating activity (MA), mitochondrial alpha-glycerophosphate dehydrogenase (alpha GPD), and/or cytosolic ornithine decarboxylase (ODC). T4 treatment caused a 28% increase in cardiac weight, about an 11-fold increase in 3',5'-T2 MA, about a 27% increase in alpha GPD activity, and about a 129% increase in ODC activity. Administration of ipodate with T4 abolished all effects of T4 on the heart. PTU abolished the effect of T4 on alpha GPD and markedly reduced its effect on 3',5'-T2 MA and ODC activity; it had little effect on cardiac hypertrophy caused by T4 treatment. Propranolol reduced the increase in cardiac weight following T4 administration from 28% to 11%, but had a modest or no effect on T4-induced changes in other metabolic variables studied. Amiodarone also reduced the effect of T4 on heart weight, but had little or no influence on 3',5'-T2 MA, the only metabolic variable studied. T3 treatment of the rat caused a 35% increase in heart weight, about a 15-fold increase in 3',5'-T2 MA, about a 35% increase in alpha GPD, and about a 100% increase in ODC activity. Ipodate and PTU reduced the increase in 3',5'-T2 MA following T3 administration, but had no appreciable influence on heart weight, alpha GPD, and/or ODC activity. Propranolol and amiodarone had no significant effect on any of the changes studied after T3 administration. It was concluded that: 1) ipodate markedly lessens or abolishes the effects of T4 on the heart; 2) propranolol and amiodarone decrease cardiac hypertrophy in response to T4 administration, but have little or no effect on metabolic changes due to T4; 3) PTU curtails the metabolic effects of T4 on the heart but has little effect on cardiac hypertrophy; 4) none of the drugs studied affects cardiac changes occurring after T3 administration. The changes observed in 3',5'-T2 MA after ipodate and PTU treatment may have been a result of direct interaction of the drugs with the deiodinase.
D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004104:Diiodothyronines / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007487:Ipodate / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
D004104:Diiodothyronines; D014284:Triiodothyronine; C030102:3',5'-diiodothyronine; D011441:Propylthiouracil; D011433:Propranolol; D005993:Glycerolphosphate Dehydrogenase; D009955:Ornithine Decarboxylase; D007487:Ipodate; D000638:Amiodarone; D013974:Thyroxine