Effects of oral propylthiouracil treatment on nitric oxide production in rat aorta

1 The effects of oral propylthiouracil (PTU) treatment on vascular nitric o xide (NO) production were studied in the rat aorta. 2 Rats were fed a standard low fat diet with or without 0.1% PTU, for 2 or 4 weeks, or for 2 weeks with additional thyroxine injections. Concentration response curves were then constructed to phenylephrine (PE) in both endoth elium-intact and denuded aortic rings from these animals and after incubati on with 0.1 mM L-N(G)nitroarginine (r-NOARG). In addition, expression of ni tric oxide synthase (NOS) was analysed in sections of aorta from PTU-treate d and control rats using rabbit polyclonal antibodies to both inducible NOS (iNOS) and endothelial NOS (eNOS). 3 Oral PTU treatment resulted in a significant reduction in both the maximu m response (control, 0.53 +/- 0.02; 2 week PTU, 0.20+/-0.07; 4 week PTU, 0. 07 +/- 0.02 g mg(-1)) and vessel sensitivity (EC50 values: control, 9.10 x 10(-8)+/-0.67; 2 week PTU, 7.45 x 10(-7)+/-1.15; 4 week PTU, 9.73 x 10(-7)/-0.45 hi) to PE in endothelium-intact vessel rings, as compared to control s (P<0.05). Both endothelial removal and incubation with L-NOARG restored t he maximum response after 2, but not 4 weeks, although, in general, vessel sensitivity was not altered by either treatment. Vessels from PTU-treated r ats given thyroxine injections showed no significant differences between an y of the dose response curve parameters. Immunohistochemical analysis sugge sted that labelling for eNOS may be increased after PTU treatment as compar ed to control animals, whereas iNOS antibody immunoreactivity was not diffe rent between the two groups. 4 These results suggest that the hyporesponsiveness to PE observed after or al PTU treatment is, in part, due to enhanced nitric oxide (NO) production by the endothelium, and demonstrate for the first time that thyroid hormone s may play a role in the regulation of eNOS activity in the rat aorta.