Acute Triiodothyronine (T3) Administration Improves Vascular Function in Dahl Salt‐Sensitive Rats

Hypertension is a debilitating disease associated with severe vascular complications including stroke and myocardial infarction. Hypertensive vascular dysfunction is comprised of both increased contractility and impaired vasodilation. Hypertensive crisis leads to vascular dysfunction that may be fatal if not treated promptly. Unfortunately, sodium nitroprusside, a first line treatment for such hypertensive emergencies, causes adverse effects in some patients. Thus, a safer, life‐saving vasoactive agent in such patients is paramount. Recent studies from our group and others have demonstrated that T3, the active form of thyroid hormone, rapidly relaxes vascular beds via non‐genomic mechanisms. Hence, we hypothesize the acute administration of T3 can improve vascular function in hypertensive animals. Female Dahl salt‐sensitive rats were given either a high NaCl (8%, hypertensive group) or low NaCl (0.3%, control group) diet for 16 weeks. Using tail‐cuff plethysmography, we confirmed a greater increase in systolic blood pressure in the hypertensive group compared with the control group (191 ± 18 mmHg vs. 138 ± 10 mmHg, p<0.05, n=7). Furthermore, we investigated the acute vascular effects of T3 utilizing aortas isolated from both groups. Aortas were treated with T3 (0.001 μM) for 20 minutes prior to functional vascular studies using wire myograph. Relaxation and contraction were measured by a concentration‐dependent response to acetylcholine (ACh) and phenylephrine (PE), respectively. Aortas from the hypertensive group exhibited a marked impairment of endothelium‐dependent relaxation (55% reduction compared with the control group, p<0.05, n=7), which was significantly improved with acute T3 treatment (45% reduction, p<0.05, n=7). Moreover, aortas from the hypertensive group showed a greater contraction with PE (19 ± 1 mN vs. 14 ± 1.2 mN control, p<0.01, n=7), which was considerably reduced with acute T3 administration (12 ± 0.9 mN, p<0.001, n=7). In addition, long‐term vascular effects of T3 on inflammatory and oxidative stress markers (NF‐κβ and p47phox, respectively) were tested by treating the groups with a low‐dose of T3 (5ug/Kg/day) in drinking water for 12 weeks. Western blot analysis revealed that vessels from hypertensive rats displayed increased expression of p47phox (50% increase vs. control, p<0.05, n=4) and NF‐κβ (75% increase vs. control, p<0.01, n=4), yet these markers were reduced in the hypertensive group treated with T3, supporting a vasculo‐protective role of T3. Taken together, our results suggest both short and long term protective effects of T3 on the vasculature of hypertensive rats, endorsing it as a potential innovative therapy for patients with hypertensive emergency or as hypertensive prophylaxis for those who don't respond favorably to the current agents. Support or Funding Information NIH 1T3 improves ACh mediated endothelium relaxation in hypertensive aortas.2(A) T3 attenuates PE‐induced over contraction in hypertensive aortas. (B) T3 did not alter PE‐induced contraction in aortas from control group.