Effect of nitrate and L-arginine therapy on nitric oxide levels in serum, heart, and aorta of fetal hypothyroid rats

J Physiol Biochem. 2013 Dec;69(4):751-9. doi: 10.1007/s13105-013-0251-x. Epub 2013 Apr 9.

Abstract

Reduced nitric oxide availability and a heterogeneous pattern of nitric oxide synthase activity in some tissues have been reported in hypothyroidism. This study aimed at determining the effects of oral nitrate and L-arginine administration on serum, heart, and aorta nitric oxide metabolite concentrations in fetal hypothyroid rats. In an experimental study, pregnant Wistar rats were administrated tap water or 0.02 % of 6-propyl-2-thiouracil in drinking water during pregnancy and their male pups were followed (n = 8/group). In adult progeny, serum, heart, and aorta nitric oxide metabolite concentrations were measured by the Griess method after 1-week administration of sodium nitrate (500 mg/L) or L-arginine (2 %) in drinking water. Serum thyroid hormone and thyroid-stimulating hormone levels were also measured. Compared to controls, fetal hypothyroid progeny had significantly lower nitric oxide metabolite concentrations in heart (0.32 ± 0.07 vs. 0.90 ± 0.14 nmol/mg protein, p = 0.004) and aorta (2.98±0.56 vs. 6.15±0.74 nmol/mg protein, p = 0.011) tissues. Nitrate therapy restored heart nitric oxide metabolite levels decreased by fetal hypothyroidism, while L-arginine administration further decreased aorta nitric oxide metabolite levels. Sodium nitrate increased and L-arginine decreased serum nitric oxide metabolite levels in both control and fetal hypothyroid animals. In conclusion, nitrate therapy restores decreased heart nitric oxide metabolite levels, whereas L-arginine decreases aorta nitric oxide metabolite levels even further in fetal hypothyroid rats, findings relevant to the cardiovascular consequences of congenital hypothyroidism in adulthood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antithyroid Agents / adverse effects
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / pathology
  • Arginine / adverse effects*
  • Congenital Hypothyroidism / chemically induced
  • Congenital Hypothyroidism / drug therapy*
  • Congenital Hypothyroidism / metabolism
  • Congenital Hypothyroidism / pathology
  • Female
  • Fetus / metabolism*
  • Fetus / pathology
  • Heart / drug effects*
  • Male
  • Nitrates / pharmacology*
  • Nitric Oxide / metabolism*
  • Pregnancy
  • Propylthiouracil / adverse effects
  • Rats
  • Rats, Wistar
  • Thyrotropin / blood
  • Thyroxine / blood
  • Triiodothyronine / blood

Substances

  • Antithyroid Agents
  • Nitrates
  • Triiodothyronine
  • Nitric Oxide
  • Propylthiouracil
  • sodium nitrate
  • Thyrotropin
  • Arginine
  • Thyroxine