title: Increased gene expression of catecholamine-synthesizing enzymes in adrenal glands contributes to high circulating catecholamines in pigs with tachycardia-induced cardiomyopathy.
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.
authors.affiliation: Regional Specialist Hospital in Wroclaw, Research and Development Centre, Wroclaw, Poland. liliana.kiczak@up.wroc.pl.
authors.forename: A
authors.initials: A
authors.lastname: Tomaszek
authors.forename: L
authors.initials: L
authors.lastname: Kiczak
authors.forename: J
authors.initials: J
authors.lastname: Bania
authors.forename: U
authors.initials: U
authors.lastname: Paslawska
authors.forename: M
authors.initials: M
authors.lastname: Zacharski
authors.forename: A
authors.initials: A
authors.lastname: Janiszewski
authors.forename: A
authors.initials: A
authors.lastname: Noszczyk-Nowak
authors.forename: P
authors.initials: P
authors.lastname: Dziegiel
authors.forename: P
authors.initials: P
authors.lastname: Kuropka
authors.forename: P
authors.initials: P
authors.lastname: Ponikowski
authors.forename: E A
authors.initials: EA
authors.lastname: Jankowska
mesh_terms: D000311:Adrenal Glands / Q000201:enzymology* / Q000378:metabolism*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000378:metabolism; D009202:Cardiomyopathies / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002395:Catecholamines / Q000097:blood*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D004837:Epinephrine / Q000097:blood; D015870:Gene Expression / Q000235:genetics*; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D013552:Swine; D013610:Tachycardia / Q000503:physiopathology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D002395:Catecholamines; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D009638:Norepinephrine; D004837:Epinephrine