Increased gene expression of catecholamine-synthesizing enzymes in adrenal glands contributes to high circulating catecholamines in pigs with tachycardia-induced cardiomyopathy

J Physiol Pharmacol. 2015 Apr;66(2):227-31.

Abstract

High levels of circulating catecholamines have been established as fundamental pathophysiological elements of heart failure (HF). However, it is unclear whether the increased gene expression of catecholamine-synthesis enzymes in the adrenal glands contributes to these hormone abnormalities in large animal HF models. We analyzed the mRNA levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AAAD), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands of 18 pigs with chronic systolic non-ischaemic HF (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 sham-operated controls. Pigs with severe HF demonstrated an increased expression of TH and DBH (but neither AAAD nor PNMT) as compared to animals with milder HF and controls (P<0.05 in all cases). The increased adrenal mRNA expression of TH and DBH was accompanied by a reduced left ventricle ejection fraction (LVEF) (P<0.001) and an elevated plasma B-type natriuretic peptide (BNP) (P<0.01), the other indices reflecting HF severity. There was a positive relationship between the increased adrenal mRNA expression of TH and DBH, and the high levels of circulating adrenaline and noradrenaline (all P<0.05). The association with noradrenaline remained significant also when adjusted for LVEF and plasma BNP, suggesting a significant contribution of adrenals to the circulating pool of catecholamines in subjects with systolic HF.

MeSH terms

  • Adrenal Glands / enzymology*
  • Adrenal Glands / metabolism*
  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / genetics
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Cardiomyopathies / blood
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • Catecholamines / blood*
  • Dopamine beta-Hydroxylase / genetics
  • Epinephrine / blood
  • Gene Expression / genetics*
  • Heart Ventricles / metabolism
  • Male
  • Natriuretic Peptide, Brain / blood
  • Norepinephrine / blood
  • Phenylethanolamine N-Methyltransferase / genetics
  • RNA, Messenger / genetics
  • Swine
  • Tachycardia / physiopathology*
  • Tyrosine 3-Monooxygenase / genetics

Substances

  • Catecholamines
  • RNA, Messenger
  • Natriuretic Peptide, Brain
  • Tyrosine 3-Monooxygenase
  • Dopamine beta-Hydroxylase
  • Phenylethanolamine N-Methyltransferase
  • Aromatic-L-Amino-Acid Decarboxylases
  • Norepinephrine
  • Epinephrine