title: Intrinsic vascular dopamine - a key modulator of hypoxia-induced vasodilatation in splanchnic vessels.
abstract: Dopamine not only is a precursor of the catecholamines noradrenaline and adrenaline but also serves as an independent neurotransmitter and paracrine hormone. It plays an important role in the pathogenesis of hypertension and is a potent vasodilator in many mammalian systemic arteries, strongly suggesting an endogenous source of dopamine in the vascular wall. Here we demonstrated dopamine, noradrenaline and adrenaline in rat aorta and superior mesenteric arteries (SMA) by radioimmunoassay. Chemical sympathectomy with 6-hydroxydopamine showed a significant reduction of noradrenaline and adrenaline, while dopamine levels remained unaffected. Isolated endothelial cells were able to synthesize and release dopamine upon cAMP stimulation. Consistent with these data, mRNAs coding for catecholamine synthesizing enzymes, i.e. tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase, and dopamine-β-hydroxylase were detected by RT-PCR in cultured endothelial cells from SMA. TH protein was detected by immunohistochemisty and Western blot. Exposure of endothelial cells to hypoxia (1% O2) increased TH mRNA. Vascular smooth muscle cells partially expressed catecholaminergic traits. A physiological role of endogenous vascular dopamine was shown in SMA, where D1 dopamine receptor blockade abrogated hypoxic vasodilatation. Experiments on SMA with endothelial denudation revealed a significant contribution of the endothelium, although subendothelial dopamine release dominated. From these results we conclude that endothelial cells and cells of the underlying vascular wall synthesize and release dopamine in an oxygen-regulated manner. In the splanchnic vasculature, this intrinsic non-neuronal dopamine is the dominating vasodilator released upon lowering of oxygen tension.
authors.affiliation: Institute for Anatomy and Cell Biology, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany.  uwe.pfeil@anatomie.med.uni-giessen.de.
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfeil
authors.forename: Jitka
authors.initials: J
authors.lastname: Kuncova
authors.forename: Doerthe
authors.initials: D
authors.lastname: Brüggmann
authors.forename: Renate
authors.initials: R
authors.lastname: Paddenberg
authors.forename: Amir
authors.initials: A
authors.lastname: Rafiq
authors.forename: Michael
authors.initials: M
authors.lastname: Henrich
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schlüter
authors.forename: Marco
authors.initials: M
authors.lastname: Mewe
authors.forename: Ralf
authors.initials: R
authors.lastname: Middendorff
authors.forename: Jana
authors.initials: J
authors.lastname: Slavikova
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kummer
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D008638:Mesenteric Arteries / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D014664:Vasodilation
chemical_list: D018492:Dopamine Antagonists; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine; D009638:Norepinephrine