Pharmacological study of the mechanisms involved in the vasodilator effect produced by the acute application of triiodothyronine to rat aortic rings

Abstract

A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8–10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5–10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.

Possible Mechanisms Involved in the Vasorelaxant Effect Produced by Anorexigenic Drugs in Rat Aortic Rings

“…According to the findings of the present study, on the other hand, fenproporex [2], amfepramone [31], clobenzorex [17] and T 3 [27] administered under certain conditions do not increase blood pressure, but instead generate endothelium-dependent vasodilation via nitric oxide, potassium and voltage-dependent calcium channels. Consequently, these drugs could probably be used without adverse cardiovascular effects [2,17,27,31]. Further research is needed to explore the possible involvement of type M1 muscarinic receptors in the mechanism of action of the aforementioned drugs, a mechanism suggested in previous reports.…”

“…There are various reports of a significantly modified cardiac function in patients with persistent subclinical thyroid dysfunction involving T 3 and/or thyroxine (T 4 ), which are thyroid hormones found in plasma and peripheral tissues, respectively. Triiodothyronine, the biological active thyroid hormone, is mostly generated by 5´-monodeiodination of T 4 in peripheral tissues [27].…”

“…Its relaxant effect was partially inhibited in the absence of endothelium and in the presence of L-NAME, TEA, atropine (a competitive nonselective antagonist at central and peripheral muscarinic acetylcholine receptors), ODQ, KT 5823, and the combination of apamin and charybdotoxin or cycloheximide. The authors suggest the possible participation of the NO-cGMP-PKG pathway and/or Ca 2+ -activated K + channels (via activation of muscarinic receptors) in the observed vasorelaxant effect [27].…”

Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility

“…Currently, there are several solubilization methods; however, determining which technique to use depends largely upon its utility within a specific assay, taking into consideration tissue and cell effects, buffer composition, and test compound polarity [3,[23][24][25][26][27]. Many organ bath studies on a variety of muscle types have used various different solvents (DMSO, EtOH, MeOH, EtAc) to solubilize test compounds [28][29][30][31][32]. However, we were not able to identify prior reports that examined the ability of various solvents and solubilization approaches that adequately solubilize compounds in the ex vivo myometrial contractility organ bath assay without affecting myometrial contractility.…”

Triiodothyronine Reduces Vascular Dysfunction Associated with Hypertension by Attenuating Protein Kinase G/Vasodilator-Stimulated Phosphoprotein Signaling

“…A series of studies has demonstrated that administration of T3 at pharmacologic concentration causes vascular relaxation (Liu et al, 2014;Samuel et al, 2017). For several years, T3-induced vascular relaxation was attributed to endothelium-dependent mechanisms (Lozano-Cuenca et al, 2016;Razvi et al, 2018), while the VSMC-related mechanisms mediating the vasodilatory effect of T3 remained understudied. In this regard, early work by Ojamaa et al (1993Ojamaa et al ( , 1996 demonstrated that T3 can directly exert its vasodilatory effect through VSMC mechanisms.…”