Comparative Study of the Effects of Acute In Vitro and Short‐term In Vivo Treatments with 3, 5, 3′ Triiodo‐L‐Thyronine on Contractile Responsiveness of Isolated Rat Thoracic Aorta

Abstract

This work was aimed to study comparatively the influences of acute in vitro and short‐term in vivo treatments with 3, 5, 3′ triiodo‐L‐thyronine (T3) on the contractile responsiveness of isolated rat thoracic aortas. Previous studies have reported that T3 through nongenomic and genomic mechanisms can elicit endothelium‐dependent and ‐independent, nitric oxide (NO)‐mediated, depression of vascular tone. Short‐term in vivo treatment (hyperthyroidism) was established by subcutaneous injections of T3 (500 mg/kg/day) for 3 days (T33d); while control rats received vehicle (alkaline saline solution) for 3 days (V3d). T33d treatment was sufficient to cause both significant weight loss and elevation of T3 serum levels in the rat. In endothelium‐intact aortic rings contracted with phenylephrine, in vitro application of increasing cumulative concentrations of T3, each 30 minutes (0.01, 0.1, 1 and 10 mM), did not alter the contractile tone compared to vehicle treated tissues. Likewise, in vitro treatment with T3 (0.1, 1 and 10 mM for 30 min or 2 hs) did not modify the relaxant responses induced by either acetylcholine or sodium nitroprusside, in that order, in endothelium‐intact and ‐denuded aortic rings contracted with phenylephrine. (In aortic rings with and without endothelium, phenylephrine‐induced precontractions were not modified by preceding exposure to T3 compared to their corresponding vehicle‐treated tissues.) The concentration‐dependent contractions caused by phenylephrine and angiotensin II in aortic rings with endothelium, remained unchanged in the presence of T3 (0.1, 1 and 10 mM) applied 30 min or 2 h before. On the other hand, T33d treatment significantly decreased the contractile responses induced by phenylephrine and angiotensin II in aortic rings with and without endothelium, related to their respective controls. The absence of endothelium or the addition of the NO synthase inhibitor, L‐NAME, in the presence of endothelium (100 mM), independently, enhanced the contractile responses to phenylephrine in aortic rings of T33d and V3d rats. However, the contractile responses to phenylephrine remained similarly depressed in endothelium‐denuded and endothelium‐intact L‐NAME‐treated aortas of T33d compared to V3d rats. In conclusion, T3 applied in vitro does not alter the development of active tone in the endothelium‐intact and ‐denuded thoracic aortas, which rules out a direct action, by a rapid non‐genomic mechanism, of this hormone in smooth muscle and endothelial cells. On the other hand, short‐term in vivo administration of T3 depressed contractile responsiveness of the thoracic aorta, independently of endothelium and NO (whether of endothelial or muscle origin). It remains to elucidate if the T3‐induced depression of aortic contractility is due to direct hormonal effects or is secondary to a hyperdynamic cardiovascular state in hyperthyroid rats.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.